Journal Pre-proof

A critical review on the applications and potential risks of emerging MoS2

nanomaterials

Zhixiang Xu, Jichang Lu, Xianyao Zheng, Bo Chen, Yongming Luo,

Muhammad Nauman Tahir, Bin Huang, Xueshan Xia, Xuejun Pan

PII: S0304-3894(20)31046-3
DOI: https://doi.org/10.1016/j.jhazmat.2020.123057
Reference: HAZMAT 123057

To appear in: Journal of Hazardous Materials

Received Date: 6 January 2020

Revised Date: 21 May 2020
Accepted Date: 25 May 2020

Please cite this article as: Xu Z, Lu J, Zheng X, Chen B, Luo Y, Tahir MN, Huang B, Xia X, Pan
X, A critical review on the applications and potential risks of emerging MoS2 nanomaterials,
Journal of Hazardous Materials (2020), doi: https://doi.org/10.1016/j.jhazmat.2020.123057

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Title Page

A critical review on the applications and potential risks of emerging

MoS2 nanomaterials

Zhixiang Xu a, b, Jichang Lu a, Xianyao Zheng a, Bo Chen a, Yongming Luo a, Muhammad Nauman Tahir a, Bin

Huang a, Xueshan Xia b, Xuejun Pan a,*

a. Faculty of Environmental Science & Engineering, Kunming University of Science and Technology, Kunming

650500, China

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b. Faculty of Life Science & Technology, Kunming University of Science and Technology, Kunming 650500,

China

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Title Page
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A critical review on the applications and potential risks of emerging

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MoS2 nanomaterials
Zhixiang Xu a, b, Jichang Lu a, Xianyao Zheng a, Bo Chen a, Yongming Luo a, Muhammad Nauman Tahir a, Bin
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Huang a, Xueshan Xia b, Xuejun Pan a*

a. Faulty of Environmental Science & Engineering, Kunming University of Science and Technology, Kunming
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650500, China

b. Faculty of Life Science & Technology, Kunming University of Science and Technology, Kunming 650500,

China

*Corresponding author: Xuejun Pan, Tel./Fax: +86 871-65920510, Email: [email protected]

Total number of Figures & Tables: 7 Figures and 8 Tables.

Grants: National Natural Science Foundation of China (grants no. 21567014, 51878321 and 51968032), China

Postdoctoral Science Foundation (grant no. 2019M653846XB), and Yunnan Provincial Department of Education

(grant no. 2020J0060).

Graphical Abstract

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Health risks
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Highlights

 MoS2 nanomaterials are widely applied in environmental protection and

biomedicine.
  Both characteristics and surrounding matrices alter MoS2' environmental

behaviors.

 Several in vitro and in vivo protocols have been studied for MoS2' potential health

risks.

 MoS2 induce toxic effects via both oxidative and non-oxidative stress manners.

 The influx of MoS2 is a matter of balancing rewards and risks in environment and

humans.

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Abstract

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Molybdenum disulfide (MoS2) nanomaterials have been widely used in various fields such as

energy store and transformation, environment protection, and biomedicine due to their unique
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physicochemical properties. Unfortunately, such large-scale production and use of MoS2
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nanomaterials would inevitably release into the environmental system and then potentially increase

the risks of wildlife/ecosystem and human beings as well. In this review, we first introduce the
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physicochemichemical properties, synthetic methods and environmental behaviors of MoS2

nanomaterials and their typical functionalized materials, then summarize their environmental and
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biomedical applications, next assess their potential health risks, covering in vivo and in vitro studies,

along with the underlying toxicological mechanisms, and last point out some special phenomena
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about the balance between applications and potential risks. This review aims to provide guidance

for harm predication induced by MoS2 nanomaterials and to suggest prevention measures based on
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the recent research progress of MoS2' applications and exerting toxicological data.

Keywords: Molybdenum disulfide; Environmental and biomedical applications; Potential health

risks; Toxicological mechanisms; Balance

1. Introduction

Owing to their unique physicochemical properties (e.g., small size, large surface area, high

surface activity and fascinating electronic/magnetic properties), nanomaterials are increasingly

produced and applied in various fields, including sustainable chemistry industry (e.g.,

environmental analysis and pollution remediation especially adsorption and catalytic degradation),

medicine (e.g., antimicrobial and diseases therapy), biosensors, cosmetics and food additives [1, 2].

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Recently, two-dimensional (2D) nanomaterials, such as graphene, boron nitride (BN), carbon nitride

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(g-C3N4), tungsten disulfide (WS2) and molybdenum disulfide (MoS2), have attracted increasing

interest because of their promising potential for application in nanotechnology [3-6]. Among these
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2D nanomaterials, MoS2 is in forefront of materials research for its various prominent chemical,
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electronic, catalytic, optical, mechanical and sensing properties [7-11]. Particularly, the few-layer

MoS2 (FLMoS2) or single-layer MoS2 (SLMoS2) nanosheets possess better properties than that of
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bulk ones, thus being isolated and used [10, 12, 13]. Unfortunately, they could suffer from rapid

re-aggregation or precipitation in normal conditions [8, 14]. The functionalized MoS2

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nanocomposites using other organic and inorganic chemicals on the basis of MoS2 nanosheets,

however, often show stronger colloidal stability along with excellent electrochemical behavior,
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catalytic performance and sensing abilities [15, 16], and therefore have being extensively

synthesized and applied in environmental monitoring, pollutants detection and removal, and
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biomedicine [7, 8, 17, 18]. Additional, MoS2-based nanomaterials show obvious suitable energy

band structures for photo-hydrogen production over that of noble metal catalysts [19], thus having

been widely used as a co-catalyst for photocatalytic hydrogen production from water [20]. All the

above constitute the sources of MoS2 nanomaterials.

Due to their growing production and large-scale use, MoS2 nanomaterials should be
consequently ubiquitous in environmental media, thus potentially increasing the risks of

wildlife/ecosystem and human beings as well [21]. Specifically, nanomaterials that do not degrade

may accumulate in the tissues and interact with surrounding cells, which in turn cause potential

adverse effects [22]. That is to say, the biodistribution and excretion of nanomaterials are important

concern when exploring their adverse effects on living organisms. Researches have demonstrated

that nanomaterials exposure is closely related to human immune diseases even induce various

malignancies. Considering that MoS2 nanomaterials are extensively used in environmental and

biomedical fields, and then released into environmental media inevitably, the determination of

potential risks associated with nano-MoS2 exposure is of fundamental importance for the translation

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of them into use.

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Previous representative reviews were concentrated on the synthetic methods and applications

of MoS2 nanomaterials, including photocatalytic hydrogen production and energy storage [19, 23],
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photocatalytic degradation of environmental pollutants [24, 25] and biosensors [26]. However, few
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reviews have focused on the MoS2 nanomaterials' potential risks along with toxic mechanisms.

Indeed, the benefits of MoS2 nanomaterials usage must be weighed against potential health and
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environmental hazards associated with their development, use and disposal. The present review

therefore aims to explore the balance between various applications and potential health risks of
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MoS2 nanomaterials based on the exerting research status and progress. First, the physicochemical

properties, synthetic methods and environmental behaviors of MoS2 nanomaterials and their
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functionalized materials are systematically introduced. Furthermore, the latest researches about their

environmental and biomedical applications along with their potential health risks, covering in vivo
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and in vitro studies, are critically summarized. Next, the underlying molecular toxicological

mechanisms are illustrated. Then, several special phenomena about the balance between

applications and risks are pointed out. Finally, a comprehensive evaluation system used in MoS2

nanomaterials' potential risk is proposed. This review provides insights into MoS2's applications and

potential health effects, thus giving guidance for harm predication and making full use of their
advantages as well.

2. Physicochemical properties, synthetic methods and environmental

behaviors of MoS2 nanomaterials

2.1. Physicochemical properties of MoS2 nanomaterials

As a type of inorganic 2D transition metal dichalcogenides (TMD), MoS2 nanomaterials have a

structure consisting of chemically bonded two-dimensional S–Mo–S nanosheets held together by

van der Waals' interactions [7, 10, 27]. Due to the presence of specific atomic assembled manner,

three crystal structures (i.e., 1T-phase, 2H-phase and 3R-phase) existed in MoS2 nanomaterials [19,

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28], as shown in Fig. 1. The 2H-phase is dominant in nature and more stable than that of 1T- and

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3R- phases [19]. Generally, 1T- and 3R- phases can easily transform into the 2H-phase. The

2H-phase can also transform into metastable 1T- and 3R- phases upon specific conditions, including
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annealing, electric doping or by controlling strain [14, 29, 30], resulting in extraordinary changes in
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their performances. For instance, the conversion of 2H-phase to 1T-phase enhances MoS2's catalytic

performances for hydrogen evolution reaction and pollutant degradation [20, 30]. Unfortunately,
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one case has suggested that such transition would increase the corresponding ecotoxicity [14].

Above results indicate that the transformation of MoS2's phases might have closely relation to their
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applications and potential risks.

Because of their unique 2D structure along with phase transition, MoS2 nanomaterials exhibit
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many fantastic physicochemical properties, namely prominent chemical, electronic, catalytic,

photoluminescent, optical and sensing performances [2, 31, 32]. The properties of MoS2
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nanomaterials are usually dependent on their layers, which often contribute to different potential

applications and toxicological behaviors. The layers are divided into two different groups, namely

the nanosheets (i.e., single-layer and few-layer) and bulk phases. Compared with the bulk MoS2,

MoS2 nanosheets exert unique photoluminescent and electronic properties [7, 32, 33]. Particularly,

SLMoS2 nanosheets have an ultra-high specific surface area, excellent biocompatibility and in vivo
biodegradability, and extinction coefficient in the near-infrared region [8, 15, 16, 34], making them

broadly used in chemical/biological sensing, bio-fluorescence imaging, drug/gene delivery and

phototherapy. In addition, MoS2 nanosheets exert superbly antifouling properties similar to that of

graphene oxide (GO) and reduced graphene oxide (RGO) [35], and thus have been widely used to

modify conductive polymer surfaces for the mitigation of fouling.

Fig. 1 Typical crystal structures of MoS2 nanomaterials

(A) Octahedral (1T-phase), (B) Trigonal prismatic (2H-phase) and (C) Trigonal prismatic (3R-phase) unit cell
structures. Reproduced with permission from Ref. [19, 28, 36].

2.2 Synthetic methods for MoS2 nanomaterials

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Different strategies, including bottom-up method and top-down method, have been used in the

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synthesis of MoS2 nanomaterials [6], as shown in Fig. 2. Generally, different synthetic methods

have their own advantages and intrinsic limitations. Among these bottom-up methods, the
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hydrothermal route is widely applied in MoS2 nanosheets synthesis for its easy operability and
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large-scale fabrication by using different precursors of Mo (i.e., (NH4)6Mo7O24, (NH4)2MoS4, MoO3

and Na2MoO4) and S (i.e., elemental sulfur, (NH4)2S2O8, NaSCN, H2NCSNH2 and CH3CSNH2)
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directly, as described in Fig. 2A. The chemical vapor deposition (CVD), of course, often shows the

highest controllability, and thus has been continuously developed and supposed as a credible and
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forceful technique for producing large amounts of ultrathin 2D nanomaterials including MoS2

nanosheets especially on SiO2 substrates under the guidance of Lee's group [6, 37]. It should be
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pointed out that the different types of precursors, reaction temperature, solvent or atmosphere adopt

in the bottom-up method would result in significant differences in the properties of these synthetic
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MoS2 nanomaterials.

Several other top-down synthesis methods, including chemical exfoliation (e.g., ion

intercalation), liquid-phase and surfactant-assisted exfoliation, and micromechanical exfoliation (i.e.,

ball-milling and sonication), have been extensively implemented to obtain such MoS2 nanosheets

from bulk-phase MoS2 indirectly [4, 16, 30, 34, 38-42]. These synthetic methods are presented in
Fig. 2B. Particularly, the chemical exfoliation has been regarded as a highly-scalable method for

bulk MoS2 exfoliation because of its higher yield and stability [7]. Various intercalating agents

especially the lithium-containing compounds, including methyllithium (Me-Li), n-butyllithium

(n-Bu-Li) and tert-butyllithium (t-Bu-Li), have been used for the chemical exfoliation of bulk-phase

MoS2 [43, 44]. Different organic lithium compounds exhibit different extent of Li intercalation,

resulting in different degrees of exfoliation. However, such exfoliation method may generate

secondary pollution and potential security risks during the operating process since

lithium-containing compounds are used. Recently, a dry ball-milling process has also been used in

MoS2 exfoliation for its simple operation procedure. Additional, it can significantly enhance the

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adsorption properties of the MoS2 without the need of any additional reaction or involvement of

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chemical agents [45]. However, the ball-milling exfoliation method shows limited usefulness in

practical applications for its lower yield and purity. These studies strongly suggest that different
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exfoliation methods can be used to prepare ultrathin 2D MoS2 nanosheets with varying structural
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features including size, thickness, crystallinity and crystal phase, which are favorable for various

applications.
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Without a doubt, those prepared MoS2 nanosheets possess a higher fluorescence yield and

greater stability than that of the bulk ones no matter what synthetic strategies are adopted [4, 46],
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thus showing excellent application prospect in sensors, electronics and catalysis [30, 41]. Further

study has found that a confinement of platinum nanoparticles within the MoS2-layered structure
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could enhance hydrogen evolution reaction activity and stability [47]. Unfortunately, these MoS2

nanosheets could suffer from rapid re-aggregation or precipitation in normal physiological

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conditions [14, 40]. To enhance their colloidal stability along with photoelectrochemical properties,

MoS2 nanosheets therefore have been chemically functionalized with other nanomaterials or

constituents to form nanocomposites, including carbonaceous materials, noble materials or organic

macromolecules (e.g., polyaniline, polyethylenimine, polyacrylic acid and polyethylene glycol) [17,

48-52], as shown in Fig. 2C and Table 1–6. For instance, the carbon nanotubes (CNTs) could
promote the electron transfer rate between electroactive species and electrodes for its high

electronic conductivity, and therefore having been used in designing electrochemical sensing

platform [53]. The functionalization can be divided into two parts, namely the covalent and

non-covalent [40]. The former based on an appropriate function reacts with the surface atoms of

MoS2 nanomaterials, whereas the latter used the surfactants or polymers to disperse the nanosheets.

Among several functionalized methods, hydrothermal routes which can be used to grow nanosize

crystalline materials under low temperature but without further annealing treatment have been

widely applied [54]. The MoS2 nanomaterials' composition and structural information, of course,

are comprehensively visualized with various appropriate characterization techniques, which helps to

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understand the correlations between structures and properties.

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Fig. 2 Typical synthetic methods of MoS2 nanosheets and MoS2-based nanocomposites

Bottom-up methods (i.e., hydrothermal (A1) and chemical vapor deposition (A2)) and top-down methods (i.e.,
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chemical exfoliation (B1), liquid-phase exfoliation (B2) and micromechanical exfoliation (B3)) used for MoS2
nanosheets synthesis; covalent (C1) and non-covalent (C2) functionalization used for MoS2-based nanocomposites
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synthesis.

2.3. Potential sources and environmental behaviors of MoS2 nanomaterials

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MoS2 nanomaterials have been widely applied in various areas, including pollution abatement,

contaminant analysis and biomedical materials [7, 17]. Those applications depend on their different
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physicochemical properties. Unfortunately, they would be released into the atmosphere and aquatic

environments unintentionally or intentionally in the course of manufacture, use or deposit [14, 21].
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Landfills are expected to receive a considerable amount of nano-MoS2 products, ultimately leaching
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into the surrounding environmental media [55, 56]. Moreover, nano-MoS2 that cannot captured by

wastewater treatment processes are released into the water bodies with effluent [57]. Aquatic (i.e.,

water and sediments) and terrestrial compartments are predicted to be the destination of the released

MoS2 nanomaterials.

Those MoS2 nanomaterials can be transformed when released into the environment [14],

making it crucial to conduct the complex interaction research between environmental matrices and
MoS2 nanomaterials. The environmental behaviors of MoS2 nanomaterials generally depend

strongly on their characteristics as well as the respective environmental conditions, including light

illumination, pH, oxygen, natural organic maters (NOM) and ionic strength [5, 14]. Those

transformations of MoS2 nanomaterials in the environment, in fact, are a result of various physical,

chemical, and biological-mediated processes [1]. The most commonly occurring physicochemical

processes are aggregation, adsorption, deposition and dissolution. Particularly, NOM such as humic

acid (HA) and fulvic acid (FA) are important components in aquatic environments, and they could

regulate the environmental transformations and biological toxicities of nanoparticles by changing

their surface properties through noncovalent interactions [21]. MoS2 nanomaterials can also be

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oxidized in the presence of oxygen or other strong oxidizing agents, leading to the release of soluble

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species [58]. Further study confirms that oxygen-containing aqueous phase with visible light

irradiation at room temperature can drive phase transition and structural alterations of MoS2
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nanosheets, despite the process is slow [14]. Above physicochemical modifications would then
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exert dual roles in toxic responses to MoS2 nanomaterials.

The biological process may also participate in the distribution, absorption and
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bio-concentration of MoS2 similar with other nanomaterials [59]. Importantly, the residual

nano-MoS2 materials in natural waters, soils and sediments would directly harm to the living beings.
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On the other hand, such nanomaterials maybe accumulated and ultimately influencing the human

health indirectly. From the above, MoS2 nanomaterials can be migrated and transformed in different
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environmental media, ultimately generate different effects on organisms.

3. Applications of MoS2 nanomaterials in environmental protection

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Due to their special layered structure, MoS2 nanomaterials have been considered as promising

candidates for environmental contaminants determination and pollution cleanup. Particularly, the

MoS2 nanosheets and MoS2-based functionalized nanocomposites have high surface areas, better

catalytic performances and good chemical stabilities than that of bulk-MoS2 ones, and thus have

been extensively implemented in the determination and removal of environmental contaminants in

both individual and simultaneous fashion. These environmental contaminants mainly contain

organic pollutants (i.e., endocrine disrupting chemicals (EDCs), organic dyes and antibiotics) and

inorganic pollutants expecially heavy metals. Those MoS2 nanomaterials are also used as

antibacterial agents to devitalize or even kill the pathogenic bacteria.

3.1. Detection of environmental contaminants

Since many analytes that existed in the complex environmental media are at very low levels,

developing more sensitive methods has become one of the most attractive subjects in analytical

chemistry [3]. With excellent electrocatalytic property, fluorescence quenching ability, and high

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selectivity, MoS2 nanosheets are getting more attention in electroanalytical chemistry [48, 60]. They

are widely used to determine the levels of different conventional and trace contaminants for their

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strong sensitivity, as shown in Table 1. The most common methods used in the determination of

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objectives at environmental levels are cyclic voltammetry (CV), differential pulse voltammetry

(DPV), electrochemical impedance spectroscopy (EIS) and fluorescence spectroscopy.

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Although emphasized in every aspect, MoS2 nanosheets tend to aggregate [8], and they possess

poor intrinsic conductivity than that of carbon-based nanomaterials [53, 61, 62], noble materials [3,
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63] or functional organic materials [51, 64]. Those defects limit their widespread applications. To

overcome these limitations, MoS2 nanosheets have been functionalized with above organic or
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inorganic compounds with controllable conductivity and high electrochemical activity, as indicated

in Fig. 2C. As an example, multiwalled carbon nanotubes (f-MWCNTs) that with negatively
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charged surfaces could be easily attached to the positively charged molybdenum precursor via

electrostatic interaction [48]. With rapid response, high stability and selectivity [65], these
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functionalized nano-MoS2 composites are widely used as photoelectrochemical sensors in the

determination of trace contaminants especially EDCs and antibiotics. For instance, the

MoS2/f-MWCNTs nanocomposites are synthesized with hydrothermal method by Govindasamy

group and applied to determine the chloramphenicol in food samples, including milk, honey and

powdered milk [48]. Inspired by this, Ma et al. assemble a large amount of signal probe Tb on the
polyethylenimine functionalized-MoS2 doped multi-walled carbon nanotubes (PEI-MoS2-MWCNTs)

to further obtain the obvious and stable variation of CV responses, realizing the quantitative

determination of zearalenone [64]. Similarly, the reduced graphene oxide/molybdenum

disulfide/polyaniline nanocomposite-based electrochemical aptasensor (RGO/MoS2/PANI@AuNPs)

shows higher sensitivity in aflatoxin B1 detection [62]. Apart from aflatoxin B1, those AuNPs/MoS2

nanocomposites are also used in the detection of other mycotoxins and EDCs like bisphenol A (BPA)

by controlling the corresponding aptamer [3, 62].

Other than trace contaminants, the MoS2 nanocomposites are also extensively applied in the

determination of conventional pollutants. For example, the Bi2O3/Bi2S3 uniformly distributed on the

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surface of the MoS2 nanosheets could provide more active sites, thus enhancing the detection

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sensitivity of the corresponding NOx gas [63]. Analogously, luminescent MoS2 nanosheet-based

peroxidase mimetics (MoS2/OPD/H2O2) could enhance the sensitivity and selectivity for the
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detection of Fe2+ in a label-free colorimetric sensor [66]. Some functionalized MoS2
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nanocomposites, of course, have been synthesized for the simultaneous determination of different

pollutants. For instance, the Fe3O4/MoS2/GCE shows excellent electrocatalytic performance and can
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be used to simultaneously determine the concentrations of nitrite and Cr6+ [38]. Therefore, we

would better identify whether other MoS2-based nanomaterials can also be used for simultaneous
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detection of multiple environemntal contaminants.

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 Table 1 MoS2 nanomaterials used in the detection of typical environmental pollutants

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Nanomaterials Synthesis Precursors Reaction Physicochemical Pollutants Detection Detection Limit of References

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methods conditions property method range detection
(LOD)
MoS2 Hydrothermal Na2MoO4·2H2O 200 ℃ for Nanoplates Tetracyclines Fluorescence 0.1–50 μM 0.032 μM [10]
and glutathione 24 h spectra
SLMoS2 Ball-milling Bulk MoS2 100 rpm for Nanosheets NH3 – In ppm – [4]
followed by 12 h range

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sonication
Fe3O4/MoS2 Hydrothermal Na2MoO4·2H2O, 200 ℃ for Nanocomposite Nitrite and Cr6+ CV 1–2630 and 5 and 0.2 [38]
H2NCSNH2 and 16 h 0.5–328 μM,
Fe3O4 μM, respectively

e-
respectively
MoS2-RuS2 One-pot RuCl3.xH2O, 200 ℃ for Nanocomposite Sulphadiazine CV 0.01–598.7 0.004 μM [60]
hydrothermal Na2MoO4·2H2O 22 h μM
and (NH2)2CS
MoS2/f-MWCNTs Hydrothermal Na2MoO4·2H2O, 200 ℃ for 3D hierarchical Chloramphenicol Amperometry 0.08–1392 0.015 μM [48]

Pr
H2NCSNH2 and 24 h nanocomposite μM
f-MWCNTs
SPAN-MoS2 Ultrasonication Bulk MoS2 and – 3D Chloramphenicol DPV 0.1–1000 0.065 μM [51]
polyaniline (PAN) interconnected μM
nanocomposite
MoS2/NGH Hydrothermal Na2MoO4·2H2O, 200 ℃ for Nanocomposite Chloramphenicol EIS and 32.3–96900 3.23 ng.L−1 [65]
l cysteine and 36 h photocurrent ng.L−1
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nitrogen doped responses
graphene hydrogels
(NGH)
CS-UCNP/MoS2 – Lanthanide ions CS-UCNPs Nanocomposite Microcystin-LR Fluorescence 0.01–50 0.002 [67]
doped upconversion incubated spectra ng.mL−1 ng.mL−1
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nanoparticles with MoS2

(UCNPs), for 10 min
polyacrylic acid and inTris-HCl
SLMoS2 buffer
AuNPs/MoS2/GCE Hydrothermal HAuCl4, NaBH4, 180 ℃ for Flower-like BPA CV and EIS 0.05–100 0.005 μM [3]
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Na2MoO4·2H2O 48 h nanocomposite μM
and L-cysteine
RGO/MoS2/PANI@AuNPs Hydrothermal GO, 200 ℃ for 3D hierarchical Aflatoxin B1 DPV 0.01–1 0.0020 [62]
and Insitu (NH4)6Mo7O24· 24 h nanocomposite fg.mL−1 fg.mL−1
polymerization 4H2O, H2NCSNH2,
anlline, (NH4)2S2O8
and AuNPs
PEI-MoS2-MWCNTs – Polyethyleneimine, Stirred at Nanocomposite Zearalenone CV 0.0005–50 0.17 [64]
MoS2 and room ng.mL−1 pg.mL−1
carboxylation temperature
 multi-walled carbon for 12 h
nanotube
(MWCNTs)

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MoS2/OPD/H2O2 Hydrothermal Na2MoO4·2H2O, 200 ℃ for Luminescet Fe2+ Multivaria e 0.1–1.4 μM 0.08 μM [66]

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H2NCSNH2 and 24 h MoS2 curve
o-phenylenediamine nanosheets resolution by
(OPD) alternating
least squares
(MCR-ALS)
and UV-vis

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spectroscopy
MoS2-Bi2O3-Bi2S3 Hydrothermal Bulk MoS2 and Two steps: 3D interlayer NOx CV and EIS 1–50 0.05 [63]
Bi(NO3)3 (1) 150 ℃ nanocomposite µg.mL−1 µg.mL−1
for 3–7 h;

e-
(2) 300 ℃
for 1 h
under Ar
gas

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3.2. Removal of environmental contaminants

In recent years, with the development of the global economy, the treatment of tremendous

contaminants has become a global priority. Numerious methods, including physical processes (e.g.,

adsorption and membrane filtration) and chemical processes (e.g., photocatalysis,

photoelectrocatalysis and heterogeneous catalysis), therefore have been used in the remorval of

environment contaminants. Owing to their high photoelectrocatalytic activity, strong adsorptivity

and low cost, MoS2 nanomaterials are widely used. Particularly, as one of the most well-known

photo-reactive substances with UV and visible light absorption properties, MoS2-based

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nanomaterials generate electron-hole pairs when excited with smaller wavelength than their band

gap energy, which in turn produce ROS to degrade the environmental pollutants. Those processes

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are represented in Fig. 3A–B. As a matter of in fact, the environmental containments would adsorb

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on the nanomaterials surface firstly. Such enhanced adsorptivity on the hybrid photocatalyst would

improve photodegradation of environmental pollutants.

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3.2.1. Physical adsorption and membrane filtration
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The adsorption processes have been reported to be the low-cost promising alternatives for the

treatment of both organic and inorganic pollutants existed in wastewater [27]. For their large
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number of adsorption sites, high surface area and strong surface adsorbability, nano-MoS2 and its

functionalized nanocomposites exert good abilities in the adsorption of organic dyes and heavy
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metals [27, 45, 54, 68, 69]. The electrostatic attraction, complexation and ion exchange to form

sulfur−metal bonding have been generally considered as the primary causes [70, 71]. The
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adsorption efficiency, of course, can vary with the physiochemical properties (i.e., morphology, size,

layers and phase) of MoS2 nanomaterials themselves, and diversified thermodynamics parameters

(i.e., pH conditions, ion strength and processing time), as summarized in Table 2.

Generally, the physiochemical properties of MoS2 nanomaterials are dependent on their

different synthesized methods, as previous reviewed [25]. Those different properties will surely

result in different disposal effects. For instance, Ma et al. have found that molybdenum disulphide
nanoflowers (MoS2NFs) synthesized hydrothermally exhibit excellent purification properties to

inorganic mercury (Hg2+) and methylmercury (MeHg+) as well [71]. Further study shows that

ball-milling process provides an original strategy to modify materials at the nanometer scale [45].

This methodology represents a smart solution for the fabrication of MoS2 nanopowders, which is

extremely-efficient in adsorbing the water contaminants. Importantly, the functionalized MoS2

nanocomposites often exert higher adsorption capacity than that of MoS2 nanosheets. A previous

study has revealed that a nitrogen-doped carbon with multi-functional groups on the MoS2

(NC-MoS2) possesses an excellent adsorption capacity for Pb2+ [69]. Likewise, the

polyvinylpyrrolidone (PVP), polyacrylamide (PAM) and sodium dodecyl sulfate (SDS) can

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intercalate molybdenum disulfide as adsorbents for enhanced adsorption of Cr6+ from aqueous

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solutions [2, 70]. Amazedly, MoS2/CeO2 nanocomposites show good selectivity to Pb2+ from the

coexisting background ions [72]. Special attention should be paid to the fact that the ionic strength
-p
and pH value obviously affect the absorption efficiency of MoS2-based nanocomposites, as
re
indicated in Table 2. Above findings can provide a new perspective for the rational design of MoS2

nanocomposites with high performance and excellent chemical stability for the removal of organic
lP

dyes and heavy metals under extreme conditions but without secondary pollution.

Apart from adsorption, laminar MoS2 nanomaterias have also been investigated as
na

nanolaminate membranes for water filtration due to their excellent flexible mechanical properties

[73-75]. For instance, the polydopamine (PDA)-modified MoS2 nanofiltration membrane (NFMs)
ur

has been firstly synthesized by Gao's group and used to filter the methylene blue and bovine serum

albumin [39]. This study gives inspiration to the development of inorganic membranes with high
Jo

performance especially high pure water permeance for water-related processes. The latest study

further indicates that hydrophobic functional groups-functionalized MoS2 membranes show high

water permeation rates but maintain high NaCl rejection [76]. Therefore, we can tune the selectivity

of nanolaminate membranes along with enhancing their stability by controlling the surface

chemistry and interlayer spacing.

Table 2 MoS2 nanomaterials used in the physical-removal of typical environmental pollutants

f
Nanomaterials Synthetic methods Precursors Reaction Physicochemic Pollutants Removal Removal Referenc

oo
conditions al property efficiency mechanisms es
(temperatu
re and
time)
MoS2 Hydrothermal (NH4)6Mo7O24·4H2O and 180 ℃ for Bilayer Methyl 90 mg.g−1 Adsorption [54]
elemental sulfur 50 h nanosheets orange (Time=30 min)

pr
MoS2 Hydrothermal Na2MoO4·2H2O and NaSCN 220 ℃ for Hollow Methyl 41.52 mg.g−1 Adsorption [27]
24 h microspheres orange (pH= 3,
Temperature=15
℃, Time=10

e-
senonds)
Ball-milled MoS2 Dry ball-milling process – 450 rpm Two-dimensio Methyl blue/ 113 and 63 Adsorption [45]
for 20–40 nal phenol mg.g−1,
h respecctively
(pH≈7.5,

Pr
Time=20 h)
MoS2-TiO2 Hydrothermal MoS2, TiO2 and thioacetamide 200 ℃ for Nanocomposit Methylene 364.56 mg.g−1 Adsorption [68]
24 h e blue (Time=600
min, )
g-MoS2 Hydrothermal MoO3 and KSCN 180 ℃ for Graphene-like Doxycycline 310 mg.g−1 Adsorption (π–π [77]
24 h nanosheets (pH=4–9, interaction,
l Time=24 h) hydrophobic
na
effect and
electrostatic
interaction)
PDADMA-MoS4 Iron (NH4)2MoS4, NaOH and Constant Amorphous Pb2+ and Hg2+ 765.9 and 1460.0 Adsorption [78]
exchange-agglomeration-pr poly(diallyldimethylammonium stirring for MoS2 mg.g−1,
ur

ecipitation chloride) (PDADMA) 12 h at nanocomposite respectively

20 ℃ (pH=5–7, m/V=
g.L−1, Time=6 h)
MoS2 Hydrothermal Na2MoO4, H2NCSNH2, 200 ℃ for Nanocomposit Pb2+ 315.2 and 333 Selective [72]
MoS2/CeO2 Ce(CH3COO)2 and NH3·H2O 24 h, e mg.g−1, adsorption
Jo

180 ℃ for respectively

6 h, (pH=2, Time=40
respectivel min)
y
NC-MoS2 Hydrothermal Bulk MoS2, glucosamine 200 ℃ for Nanocomposit Pb2+ 439.09 mg.g−1 Adsorption [69]
hydrochloride, 12 h e (pH=5,
1-butyl-3-methylimidazolium Time=30min)
hexafluorophosphat and Na2CO3
MoS2 Hydrothermal Na2MoO4, CH3CSNH2 and 180 ℃ for Nanocomposit Cr6+ 142.2 mg.g−1 Adsorption [70]
PVP/MoS2 polyvinylpyrrolidone (PVP) 30 h e (pH=5, I=0.01 M
 NaCl, m/V=0.5
g.L−1, Time=12
h)

f
PAM/MoS2 Hydrothermal Na2MoO4, CH3CSNH2 and 180 ℃ for Nanocomposit Cr6+ 84.9 mg.g−1 Adsorption [70]

oo
polyacrylamide (PAM) 30 h e (pH=5, I=0.01 M
NaCl, m/V=0.5
g.L−1, Time=12
h)
MoS2 Hydrothermal Na2MoO4, CH3CSNH2 and sodium 180 ℃ for Nanocomposit Cr6+ 41.84 and 63.92 Physisorption [2]
SDS-MoS2 dodecyl sulfate (SDS) 24 h e mg.g−1, and

pr
respectively chemisorption,
(pH=5, I=0.01 M respectively
NaCl, m/V=0.5
g.L−1, Time=12

e-
h)
MoS2NFs Hydrothermal (NH4)2MoS4 and poly vinyl 200 ℃ for Nanoflowers Hg2+ and Kd=9.71×107 Adsorption (I. [71]
alcohol (PVA)-based aerogel 24 h MeHg+ mL.g−1 for Hg2+, Strong chelating
over 90% interactions

Pr
removal rate for between Hg and
MeHg+ sulphur; II. ion
exchange
between Hg and
oxygen-containi
ng groups)
RGO Modified hummer's GO, MoO3·H2O, H2NCSNH2, and 550 ℃ for Nanocomposit Cd2+ and 824 and 447.9 Adsorption [79]
MoS2 method l N2H4·2H2O 6 h (Ar) e Hg2+ mg.g−1,
na
RGO-MoS2 (1:1) Chemical vapor deposition Sonicated respectively
Ultrasonic dispersion 40 min
PDA-MoS2 Presure-assisted Polydopamine (PDA) and MoS2 MoS2 Nanofiltration Methylene Rejection Nanofiltration [39]
self-assembly process nanofiltration membrane loading of membrane blue reaches 100%
0.1103 with molecular
ur

mg.cm−2 weight cutoff

for 4 h approximately
671 Da and a
high
permeability of
Jo

salts
Hydrophobic functional – – – Nanolaminate Micropollutan >90% and ~87% Nanofiltration [76]
groups-funcationlized-M membrane ts and NaCl rejection for (Methyl
oS2 membranes micropollutants functionalized
and NaCl, nanosheets
respectively show high water
permeation rates
but maintain
high NaCl
rejection)
3.2.2. Catalytic degradation

Except for strong adsorption and membrane filtration capacities, MoS2 nanosheets also act as

potential photo-catalyst under visible light irradiation for their appropriate band structures [19, 32].

With semiconductor properties, the photogenerated electrons (e−) and holes (h+) can react with

dissolved oxygen and H2O to form reactive oxygen species (ROS), including singlet oxygen (1O2),

hydroxyl peroxide (HO2•), superoxide free radical (•O2−), hydroxyl radical (•OH) and hydrogen

dioxide (H2O2). The holes in the valence band (VB) and electrons in the conduction band (CB)

exhibit high oxidizing and reducing power, respectively. Therefore, those holes and ROS especially

of
•OH can then oxidize many organic compounds to intermediate products or even CO2 and H2O,

whereas the heavy metals ions (Mm+) from waste water would be reduced after obtaining

ro
photogenerated electrons or •O2− [80-84]. These processes are shown in Fig. 3A–B and equations
-p
(1)–(15). Different from the photocatalysis, the heterogeneous catalysis acts as the most promising

methods in removing gaseous pollutants [85].

re
MoS2 + hv → MoS2 + h+ + e− (1)
lP

H2O + h+ → •OH + H+ (2)

OH− + h+ →•OH (3)

2H2O + 2e− → H2 + 2OH− (4)

na

O2 + e− → •O2− (5)

•O2− + h+ →O21 (6)

ur

•O2− + H+ → HO2• (7)

Jo

2HO2• + e− → •O2− + H2O2 (8)

HO2• + H+ + e− → H2O2 (9)

•O2− + 2H2O → 4•OH (10)

H2O2 + e− → •OH + OH− (11)

n•O2− + Mm+ → M(m−n)+ + nO2 (12)

ne−+ Mm+ → M(m−n)+ (13)

ROS (•O2−/•OH/O21…) + Organic pollutants → Intermediate products → CO2 + H2O (14)

h+ + Organic pollutants → Intermediate products → CO2 + H2O (15)

Fig. 3 ROS-mediated environment pollutants degradation and sterilization by MoS2

nanomaterials

(A) The formation approaches of reactive oxygen species (ROS) by MoS2 nanomaterials under light illumination
conditions, (B) ROS promote environmental pollutants degradation, (C) MoS2 nanomaterials used in antisepsis,
(D) MoS2 nanomaterials used in ARGs removal.

3.2.3.1 Photocatalysis

of
Photocatalysis has been extensively applied in hydrogen production, environmental

remediation, and photosynthesis. Due to the excellent optical properties, high mobility of charge

ro
carriers and better chemical stability, MoS2 nanomaterials are widely used in photocatalytic

-p
applications since they generate several active oxygen radicals. Among these active oxygen radicals,

•O2− and •OH play key parts in the photocatalytic process [86]. Herein, it should be noted that the
re
bulk MoS2 only has a small indirect bandgap (1.3 eV) which is not sufficient to induce

photocatalytic reactions and not beneficial for the separation of charge carriers. After being
lP

exfoliated to MoS2 nanosheets, the indirect bandgap transfers to a direct bandgap of 1.9 eV, and

thus showing promising visible light-responsive photocatalytic activity [24]. However, the
na

photocatalytic property of MoS2 has not been widely applied in industry for its nature of rapid

recombination of photoinduced electron-hole [87]. To overcome these problems, the construction of

ur

unique structures of MoS2-based nanocomposites to improve the charge carriers' separation and
Jo

photocatalytic stability has been widely used in the design of photocatalysts. It has been found that

an addition of hole scavengers could reduce the hole and then inhibit such recombination

sequentially, which increases the number of electrons and expedites photoreduction. On the other

hand, the oxygen vacancies such as •O2− can reduce electron-hole recombination by quickly

removing the electrons [88]. Importantly, constructing MoS2-based nanocomposites by modifying

MoS2 nanosheets with other semiconductor nanomaterials, including C3N4, TiO2, ZnO, CeO2, WO3,
ZnS, WS2, BiVO4 and graphene derivatives, to form hetero-structures could also remarkably

improve charge separation of the photogenerated electrons and holes [81, 86, 89-91], which will

result in enhanced photocatalytic activity on pollutants degradation, as indicated in Table 3. For

instance, a uniform distribution of ZnO particles on the large surface of MoS2 nanosheets could

boost the electron-hole separation ability, resulting in enhanced photocatalytic activity and

considerable stability for the photodegradation of phenol red as compared with pristine MoS2 and

ZnO under both UV and visible light irradiation [81]. An extra addition of chemical oxidants, such

as persulfate (PS), peroxymonosulfate (PMS) and H2O2, can remarkably promote MoS2'

photocatalytic performance [86, 90, 92, 93]. PS and PMS are typical precursors to generate •SO4−,

of
as indicated in equations (16)–(19). The •SO4− often exerts stronger oxidizing properties and longer

ro
lifetime than that of •O2− and •OH [86], thus exerting excellent photocatalytic activities for the

removal organic compounds. Analogously, the additional H2O2 can react with electrons and holes to
-p
form •OH to degrade environmental pollutants [90], as illustrated in equations (3) and (11). The
re
particle size and dispersibility of photocatalysts also affect their photocatalytic activity. In addition,

the MoS2 nanosheets can provide sufficient surface for direct attachment of other nanoparticles,
lP

such as ZnO [81] and TiO2 [94], thereby enhancing the photocatalytic activity. The excellent

photogenerated carriers' separation makes the MoS2-based photocatalyst as a promising candidate in

na

the practical applications.

S2O82− + hv → 2•SO4− (16)

ur

HSO5− + 2H+ + 2e− → HSO4− + H2O (17)

•O2− + HSO4− + 3H+ + 2e− →→→ •SO4− + 2H2O (18)

Jo

•OH + HSO4− → •SO4− + H2O (19)

Other than organic pollutants, MoS2-based photocatalysts have also been widely used in the

treatment of inorganic pollutants, including heavy metals especially Cr6+ as well as gas (i.e., NOx

and CO2), as shown in Table 3. For instance, the CeO2/MoS2 ternary nanocomposites show high

visible light-driven photocatalytic performance on Cr6+ reduction [91]. Similar better photocatalytic
performance has also been found in the core-shell structural p-n heterojunction photocatalyst

n-BiVO4@p-MoS2 [95]. For gas purification, a recent study has found that the MoS2/TiO2

heterojunction composite exhibits excellent photocatalytic reduction performance on CO2 into CO

and CH4 under visible light irradiation [94]. In particular, a slight increase of MoS2 content is

beneficial to the photocatalytic activity, whereas further increase of MoS2 content could block the

activity because of an inhibition of light absorption. Similarly, the MoS2/g-C3N4 hybrid

photocatalyst are also found to effectively promote the separation of the photogenerated

electrons-holes, and the separated electrons on the MoS2 surface would combine with adsorbed O2

to formed •O2− to oxidize NO into NO3− [96]. Compared with the bare g-C3N4 group, the NO

of
removal efficiency is enhanced by 65% when setting the weight content of MoS2 at 1.5 wt%. Above

ro
studies all indicate that the MoS2 content in nanocomposites significantly influence the

photocatalytic performance of environmental pollutants.

-p
To sum up, these unique properties and good performance of MoS2-based photocatalysts in the
re
degradation of different environmental pollutants suggest them to be a promising photocatalyst.

Nevertheless, the development of MoS2-based photocatalysts is still in its infancy from a practical
lP

point of view. Currently, although a few preliminary studies have investigated the influence of the

morphology on photocatalytic activity, the insights of these effects on edge sites and surface
na

properties (e.g., defects and surface charge) still need to be further explored. Importantly, since the

environmental conditions are very complex, there still many problems with the photocatalysis
ur

degradation of actual pollutants using those MoS2-based nanocomposites.

3.2.3.2 Photoelectrocatalysis
Jo

According to the latest research [97], the MoS2-based nanocomposites also exhibit excellent

photoelectrocatalytic performance and stability in the degradation of environmental pollutants when

used as electrode materials. They point out that the 3D-MoS2/1D-TiO2 nanotube arrays (NTAs)

hierarchical electrode shows effectively photoelectrocatalytic removal of levofloxacin by

broadening the absorption spectrum response range and by promoting rapidly electron-hole pairs
separation. Though little research has been carried on MoS2-based photoelectrocatalysis, the

photoelectrocatalysis can still be regard as a promising approach to removal the environmental

pollutants for their excellent electronic conductivity and photocatalytic activity.

3.2.3.3 Heterogeneous catalysis

Previously, we also investigated the applications of MoS2 nanomaterials on catalytically

converting gaseous sulfur-containing pollutants. The related researchers found that the synergetic

roles of MoS2 nanosheets with alkali metal (Na, K, Cs) can promote the conversion CO with H2S

into chemical intermediate, methanethiol, while pure MoS2 nanosheets would only generate new

S-containing pollutants (COS), indicating the additive-dependent MoS2 catalytic performance [98,

of
99]. The different additives of alkali metals (Na, K, Cs) could modify the chemical and electronic

ro
environment of the active MoS2 sites, resulting in the generation of distinguished catalytic

performance [99]. Importantly, the atomic structure of MoS2 can be controlled by alkali metal
-p
assisted with the varied annealing temperature. Two active species, 2H-MoS2 and 1T-MoS2, are
re
detected to be presented in the reaction process [100]. However, they exhibit distinct difference in

the catalytic activity, which is originated from the difference in the internal structure between two
lP

MoS2 species [100]. The long-time annealing treatment could induce the complete conversion of

1T-MoS2 into 2H-MoS2, which can be stably presented in the process of catalytic reaction,
na

indicating the unstable property of MoS2 under the high-temperature heat treatment (400 ℃).

Further investigation of the size effect of the MoS2 prepared by facile microwave method reveals
ur

that MoS2 with few layers (2-4) has the far higher catalytic activity than that of MoS2 with stacked

layers (7-10), suggesting the size-dependent MoS2 catalytic performance. It is clarified that the
Jo

additive, the crystalline structure and the nanosheets layers can largely influence the catalytic

performance of MoS2 nanosheets. However, these MoS2 nanomaterials still possess several

disadvantages such as lower activity than that of the noble metal catalysts and high resistance to

sulfur poisoning productivities in catalyst systems, in spite of little toxicity than that of the prepared

ones [85]. With that in mind, nanostructured MoS2-based nanocomposite that showed higher
specific surface area and more active sites as compared with the bulk counterpart can overcome

these defects.

of
ro
-p
re
lP
na
ur
Jo
Table 3 MoS2 nanomaterials used in the catalytic degradation of typical environmental pollutants

f
Nanomaterials Synthetic methods Precursors Reaction Physicochem Light Pollutants Initial Operation Removal Removal mechanisms Refere

oo
conditions ical property sources concentra al efficiency (Ractive radicals) nces
(temperature tions conditions (%)
and time) (catalyst
concentrat
ions, time
and pH)

pr
MoS2/BiVO4 Hydrothermal Na2MoO4·2H2O, 180 ℃ for Heterojuncti Visible Methylen 40 mg.L−1 (100/100) 94.2% Enhanced separation [87]
CH4N2S, NH4VO3 24 h for on light (500 e blue mg.mL−1 (First of photogenerated
and Bi(NO3)3 MoS2 nanocomposi W Xe 120 min run) and electron-hole pairs
100 ℃ for te lamp, λ > 89.5% (•OH and •O2−)

e-
22 h for 400 nm) (Forth
BiVO4 and cycle)
MoS2/BiVO
4
MoS2/ZnO One pot Zinc nitrate hexa 140 ℃ for 2 Heterojuncti UV Phenol 10 ppm (20/30) 93% with Enhanced [81]

Pr
hydrothermal hydrate, h on (Mercury red mg.mL−1 50 min photocatalytic
bis-hexamethylenet nanocomposi vapor under UV activity and
etramine and MoS2 te lamp) and irradiatio considerable stability
particles visible n for the
light 90% with photodegradation
(natural 80 min (•OH and •O2−)
l sun light) under
na
visible
light
irradiatio
n
MoS2 Hydrothermal for Na2MoO4·2H2O, 180 ℃ for Heterojuncti Visible Rhodamin 10 mg.L−1 (100/100) 20% and Enhanced separation [101]
mg.mL−1
ur

(0.5%−1.0%) MoS2 CH4N2S 24 h on light (300 B 99%, of photogenerated

MoS2-Bi2WO6 Bath sonication Ultrasonicat nanocomposi W halogen 60 min respectiv electron-hole pairs
for MoS2-Bi2WO6 ed for 2 h te tungsten ely (•OH, •O2− and •O2H)
projector
lamp lamp,
Jo

λ > 410
nm, 100
mW.cm−2)
g-C3N4 Thermal Melamine powders, Ultrasound Binary Visible Rhodamin 10 mg.L−1 (40/80) 62.3%, Enhanced [89]
g-C3N4/GO condensation GO and bulk MoS2 (3 h)→heat heterojunctio light (Xe B mg.mL−1 68.1%, photoelectrons and
g-C3N4/MoS2 Exfoliation (80 ℃)→dry n lamp, λ > 2.5 h 73.8% separation of
g-C3N4/MoS2/G Microwave ing (50 ℃ nanocomposi 400 nm, and photogenerated
O (200:2:1) assisted liquid for 12 h) te 100 89.5%, electron–hole pairs
assemble mW.cm−2) respectiv (•OH and •O2−)
ely
Ag/MoS2 Calcination for Na2MoO4·2H2O, 550 ℃ for 3 Ternary Visible Rhodamin 20 ppm (100/100) 31.18%, Enhanced [20]
(0.05:1) g-C3N4 CH4N2S, h in alumina nanocomposi light (300 B mg.mL−1 66.47% photoelectrons and
g-C3N4/MoS2 Hydrothermal for Na2SiO3·9H2O, crucible te W Xe 60 min and separation of

f
(0.02:1) g-C3N4/MoS2 g-C3N4 and AgNO3 220 ℃ for lamp, λ > 100%, photogenerated

oo
g-C3N4/Ag/MoS Photodeposition (1 mg.L−1) 24 h 420 nm, respectiv electron–hole pairs
2 g-C3N4/Ag/MoS2 172 ely (•OH and •O2−)
mW.cm−2)
WO3@MoS2 One-pot Na2WO4·2H2O, Ultrasound Ternary Visible BPA 10 mg.L−1 (40/50) 92.51% Enhanced separation [86]
WO3@MoS2/Ag hydrothermal for Na2MoO4·2H2O, and stirring nanocomposi light (Xe mg.mL−1 efficiency of
WO3@MoS2 CH4N2S and (overnight te (hollow lamp, λ > 140 min photoinduced

pr
Microwave AgNO3 in the tubes) 420 nm, pH=9.0 electron–hole pairs
assisted liquid dark)→irrad 2000 CPMS=1 (•OH, •O2− and
assemble for iation (1 h mW.cm−2) g.L−1 •SO4−)
WO3@MoS2/Ag under UV

e-
light)
Attapulgite-CeO Microwave Attapulgite, Microwave Ternary Visible Dibenzoth − H2O2 (30 95% Attapulgite possesses [90]
2/MoS 2 (4:10) assisted liquid Ce(NO3)3·6H2O, (100 ℃ for nanocomposi light (Xe iophene wt%) outstanding
assemble for C6H12N4, C2H5NS 20 te lamp, λ > 3h adsorption property,

Pr
Attapulgite-CeO2 and min)→dryin 420 nm, CeO2/MoS2 promotes
Hydrothermal for Na2MoO4·2H2O g (70 ℃ for 2000 separation of
Attapulgite-CeO2/ 6 mW.cm−2) photoinduced
MoS2 h)→calcine electrons–hole pairs
d (400 ℃ for (•OH)
4 h)
Hydrotherm
l al (240 ℃
na
for 2 h)
TiO2@MoS2 Hydrothermal for Na2MoO4·2H2O, 220 ℃ for Three-dimen Visible Methyl 2.5 (250/500) > 92% Enhanced separation [84]
Ag3PO4/TiO2@ TiO2@MoS2 C2H5NS, TiO2 24 h sional light (Xe orange mg.L−1 mg.mL−1 efficiency of
MoS2 (1.0−8.0 Chemical nanofibers, AgNO3 nanocomposi lamp, λ > and 12 and 5 electron-hole pairs
wt%) deposition for and Na3PO4·12H2O te 420 nm, methylene min, and excellent
ur

Ag3PO4/TiO2@M 2000 blue respective antiphotocorrosionper

oS2 mW.cm−2) ly formance (•OH)
CeO2/MoS2 Hydrothermal Ce(NO3)3·6H2O, 200 ℃ for Heterojuncti Visible Cr6+ 5 ppm (6/20) 100% Adsorption (S-rich [91]
(C6H9NO)n, 20 h on light (500 mg.mL−1 edges) and
Na2MoO4·2H2O nanocomposi W halogen 120 min photocatalytic
Jo

and CH4N2S te tungsten reduction (e−)

projector
lamp, λ >
420 nm)
n-BiVO4@p-Mo Hydrothermal Bi(NO3)3·5H2O, 200 ℃ for 3D Visible Crystal 15 and 25 (20/50) 76.5% High specific surface [95]
S2 (10 wt%) NH4VO3, 24 h heterojunctio light (500 violet and mg.L−1, mg.mL−1 and area and enhanced
Na2MoO4·2H2O n W Xe Cr6+ respective 120 min 100%, separation of
and CH4N2S nanocomposi lamp, λ > ly respectiv photogenerated
te 420 nm, ely electron-hole pairs
100 (•OH, h+ and e−)
 mW.cm−2)
MoS2/TiO2 One-step Na2MoO4·2H2O, Hydrotherm Heterojuncti Visible CO2 99.99% (50/100) MoS2/Ti Enhanced separation [94]
hydrothermal→ca CH4N2S, C6H8O7 al (240 ℃ on light (300 (100 kPa) mg.mL−1 O2 of photogenerated

f
lcined and titanium for 24 nanocomposi W Xe 6h promotes electron-hole pairs

oo
dioxide (P25) h)→calcine te lamp) the
d (300 ℃ for photocata
4 h with Ar lysis of
gas) CO2 into
CO and
CH4

pr
MoS2/g-C3N4 Hydrothermal→ul Na2MoO4·2H2O, Hydrotherm Heterojuncti Visible NOx (NO 100 ppm (200/50) 51.67% Separated electrons [96]
(0.5−5.0 wt%) trasonic C2H5NS and al (200 ℃ on light (500 and NO2) mg.mL−1 on the surface of
dispersion g-C3N4 for 16 h) nanocomposi W 30 min MoS2 combine with
→ultrasonic te high-pressu adsorbed oxygen to

e-
dispersion re Xe lamp, formed •O2− which
(2 h) λ > 400) could oxidize the
adsorbed NO to form
NO3−
200 ℃ for

Pr
MoS2/TiO2 Hydrothermal Na2MoO4·2H2O 3D/1D Visible Levofloxa 10 mg.L−1 Effective 100% Facilitated interfacial [97]
NTAs electrode assisted and TiO2 NTAs 24 h nanotube light (500 cin and area charge transfer and
anodization electrode arrays W methylene (4 cm2) enhanced separation
self-assembled hierarchical high-pressu blue Electrolyt efficiency of
approach electrode re Xe lamp, (0.01 M electron-hole pairs
λ > 420 Na2SO4 (•OH and •O2−)
nm, 33 solution)
l mW.cm−2) Bias
na
potential
(0.3 V)
180 and
150 min,
respective
ur

ly
Fe0 droped Hydrothermal→ul g-C3N4, 210 ℃ for Heterojuncti Visible Rhodamin 20 ppm (30/50) 98.2% Enhanced separation [102]
g-C3N4/MoS2 trasonic (NH4)6Mo7O24·4H2 24 h on light (500 B and mg.mL−1 and of photogenerated
dispersion O, CH4N2S, nanocomposi W Cr6+ 120 min 91.4%, electron-hole pairs
FeCl3.6H2O and te high-pressu respectiv (•O2−, h+ and e−)
Jo

NaBH4 re Xe lamp, ely

λ > 420
nm, 33
mW.cm−2)
3.3. Antibacterial agents

Previous study has revealed that MoS2 and WS2 nanomaterials could cause the oxidation of

glutathione, thereby exhibiting antimicrobial activity against both gram-negative and gram-positive

bacteria [103, 104]. Generally, MoS2 shows more efficient antimicrobial activity than that of WS2

[104]. It should be realized, of course, that MoS2 exhibits weaker antibacterial properties than that

of the currently used small molecule-based antibiotics, and thus a much higher dosage of MoS2

should be taken to achieve good sterilizing effects. The misuse and overuse of antibiotics would

greatly expedite the development of antibiotic resistant bacterial (ARB) and antibiotic resistant

of
genes (ARGs) although they sometimes exert higher antimicrobial performance [68, 105, 106].

Those ARB and ARGs are serious problems faced in the modern medical circle as it endangers

ro
human health and survival [106]. The application of nanomaterials, however, would properly solve

-p
these problems. Specifically, the metallic edges and defects on the MoS2 nanosheets exhibit

effective antimicrobial activity with efficiency exceeding that of the traditionally used agents such
re
as nano-silver [107]. In addition, nanomaterials with antibacterial activities have the potential to

reduce and eliminate the evolution of more resistant bacteria since they target multiple
lP

biomolecules, thus avoiding the development of resistant strains [105]. The antibacterial efficiency

primarily depends on the light-activated potential of ROS generation, such as H2O2, •OH, O2•− and
na

1
O2 [104, 108-111]. Specifically, SLMoS2 nanosheets present higher electron conductivity than that

of annealed exfoliated MoS2, and therefore accelerating the generation of ROS [32]. As an example,
ur

Yang and co-workers have studied the antibacterial activity of chemically exfoliated MoS2

(Ex-MoS2), and found that Ex-MoS2 significantly reduced the viability of E. coli DH5α by 90%
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compared to that of the bulk MoS2 when exposed for 2 h at 80 µg.mL−1 [110]. Similarly, the

few-layered vertically (FLV)-aligned MoS2 films along with visible light leads to a 15 times better

log disinfection compared with that of bulk MoS2 [80]. Moreover, a 5 nm copper film coated on

FLV-MoS2 results in a further six-fold sterilization efficiency since it facilitates electron–hole pair

separation and promotes the generation of ROS [80].

 Other than single-component nano-MoS2, the functionalized-MoS2 nanomaterials have also

been synthesized by decorating with some other nano-bactericides (i.e., silver, TiO2 and ZnO) and

used for disinfection, as shown in Table 4. Those functionalized-MoS2 nanocomposites often

exhibit better sterilizing effects than that of the single-component ones due to an improvement of

the separation of photogenerated electrons and holes. A group led by Awasthi has synthesized

MoS2/ZnO nanocomposites by coating flower-like ZnO on the surface of layered MoS2, and shows

that MoS2/ZnO nanocomposites significantly enhance the antibacterial activity in comparison with

pristine MoS2 and ZnO [81]. Similar phenomena have been also discovered in other MoS2-based

nanocomposites [31, 68]. Recently, MoS2 QDs-interspersed Bi2WO6 heterostructure via a bath

of
sonication method exhibits synergetic effects on photocatalytic disinfection [101]. Tang et al.

ro
demonstrate that MoS2 nanosheets vertically coated on TiO2 can promote the release of MoO42− and

generation of MoS2-inspired ROS, resulting in excellent antibacterial efficacy in Escherichia coli

-p
and Staphylococcus aureus even under dark conditions [31]. Moreover, the released Mo ions may
re
interact with the membrane proteins, and then induces structural deformation of cell membrane [111,

112]. Therefore, the antimicrobial efficacy of MoS2 nanomaterials is a combined effect of ROS
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generation and ion release (Fig. 3C). To our knowledge, there is no relevant studies have been

conducted yet in exploring the removal of ARGs by MoS2-based nanomaterials. However, previous
na

studies have shown that GO could effectively remove the ARGs by adsorption and photocatalysis

[113, 114]. As Graphene-like nanomaterials, MoS2 may reduce the ARGs pollution (Fig. 3D),
ur

whereas its removal performance should be further explored.

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Table 4 Different MoS2 nanomaterials used in antisepsis

f
Physiochemical Microbial Assessment References
Nanomaterials Methods Doses Timing Outcomes Mechanisms

oo
characteristics source endpoints
SLMoS2 Single-layered Escherichia Bacterial Plate agar 10–200 1–3 h SLMoS2 inactivate SLMoS2 acts as [32]
nanosheets coli growth assay µg.mL−1 65% of mature photocatalytic
Escherichia coli antimicrobial materials
biofilms under visible light in the
presence of

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ethylenediaminetetraacetic
acid (EDTA) as an
electron donor
Ex-MoS2 2D chemically Escherichia Cell viability, XTT and 5–80 2–6 h Ex-MoS2 shows Ex-MoS2 has higher [110]

e-
exfoliated MoS 2 coli oxidative GSH µg.mL−1 stronger antimicrobial oxidation capacity and
nanosheets stress and oxidation activity than that of more ROS generation
ROS assays the raw MoS2 powders
generation
FLV-MoS2 Few-layered Wastewater – – 1.6 20 min Over 99.999% MoS2 bandgap increased [80]

Pr
vertically µg.mL−1 inactivation of from 1.3 to 1.55 eV,
aligned bacteria under leading to FLV-MoS2
nanofilms simulated visible light generated more ROS for
bacterial inactivation
MoS2-Bi2WO6 MoS2 quantum Escherichia Bacterial Plate agar 1.0 18 h and 3 The composites Improved separation [101]
dots-interspersed coli colonies assay µg.mL−1 day exhibit excellent efficiency of
Bi2WO6 l activity in photogenerated electrical
na
heterostructure photocatalytic carriers after the
disinfection; formation of
The bacteria are MoS2-Bi2WO6 p-n
completely inactivated heterojunction
after 3-day
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photocatalysis
MoS2/TiO2 MoS2 vertically Escherichia Bacterial SEM – 6h Vertically aligned Release of MoO42− and [31]
coated on TiO2 coli and colonies morphology MoS2 on titanium generation of
Staphylococcus exerts excellent MoS2-inspired ROS
aureus activity against both
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Escherichia coli and

Staphylococcus
aureus under dark
conditions
MoS2/TiO2 Nanocomposite Escherichia Bacterial Plate agar 0–200 1h Strong antibacterial Increased ROS generation [68]
coli and colonies assay and µg.mL−1 activity against both and LDH release
Staphylococcus SEM Staphylococcus
aureus morphology aureus and
Escherichia coli
RGO-MoS2-Ag Nanocomposite Escherichia Bacterial Plate agar 0–30 1h RGO-MoS2-Ag Bacterial cell membrane [115]
 coli and colonies assay µg.mL−1 nanocomposite damage and ROS
Staphylococcus exhibites better generation
aureus antibacterial activity

f
towards Escherichia

oo
coli and
Staphylococcus
aureus than RGO,
MoS2, or rGO-MoS2
PDDA-Ag+-Cys-MoS2 Nanocomposite Escherichia Bacterial Live/dead 0–30 12 h PDDA-Ag+-Cys-MoS2 Increasing accessibility of [116]
coli and colonies staining µg.mL−1 exerts enhanced released Ag+ and ROS

pr
Staphylococcus analysis, broad-spectrum generation
aureus solid antibacterial activity
medium than that of silver
culture and nitrate

e-
SEM
morphology
MoS2/ZnO Nanocomposite Escherichia Bacterial Plate agar 0.4 11 h MoS2/ZnO Increased ROS generation [81]
coli colonies assay mg.mL−1 nanocomposites exert and surface area

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improved antibacterial
activities against the
gram-negative
Escherichia coli
bacteria compared to
pristine ones
nisin@PEGylated Conjugates Escherichia Bacterial Optical 10–40 4 h-interval nisin@PEGylated Sharp edges puncture into [11]
MoS2 l
coli and reproduction density and µg.mL−1 for 24 h MoS2 displayed the cell membranes
na
Staphylococcus and SEM antibacterial activity Intracellular ROS
aureus morphological morphology against both generation
changes gram-positive and
gram-negative
bacteria
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poly(ChCl-AA Conjugates Escherichia Bacterial Plate agar 0.001– 24 h poly(ChCl-AA Antibacterial properties of [117]
DES)@Fe3O4@MoS2 coli, colonies assay 0.003 DES)@Fe3O4@MoS2 quaternary ammonium
Pseudomonas µg.mL−1 inhibits cell growth in group in ChCl;
fluorescens, the order of Nanomaterilas disrupt the
Staphylococcus Staphylococcus cytoplasmic membrane
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aureus and aureus > Escherichia and release the

Bacillus coli > Bacillus constituents
subtilis subtilis
4. Applications of MoS2 nanomaterials in biomedical fields

A number of biomedical applications have been proposed for MoS2 nanomaterials, with the

largest set of studies focusing on fluorescence-based biomolecular sensing, drug delivery,

photothermal therapy, and bio-fluorescence imaging.

4.1. Biosensors

ROS are important second messengers indispensable in several physiological processes and are

thought as key signals of apoptosis [118, 119]. Particularly, human cancer occurs when the redox

balance is aberrant [120]. An accurate detection of the ROS levels, therefore, is of critical

of
significance in healthy control and disease treatment. As a product of incomplete reduction of O2,

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H2O2 is one of the most common ROS and it generates as a byproduct of a wide range of biological

processes [12]. Since MoS2 nanosheets possess an intrinsic peroxidase-like activity, they can
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catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction and

thus have been applied to detect the levels of H2O2 with a LOD at 2.5 nM [12, 121]. Further studies
re
demonstrate that MoS2 nanosheets functionalized with metallic or nonmetallic materials could
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improve their catalytic activities on TMB. For instance, the polyethylene glycol (PEG)-modified

MoS2 nanosheets (PEG-MoS2) have better peroxidase-like catalytic activity than that of unmodified

MoS2 nanosheets [16]. Similar better catalytic activities are also found in SDS-MoS2 [122] and
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PVP-MoS2 nanocomposites [123]. For their high sensitivity, such enzyme-mimic nanomaterials

could be useful tools for medical diagnosis. Compared with SDS-MoS2 and PVP-MoS2, PEG-MoS2
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possesses good water dispersibility and biocompatibility [16]. In addition, PEG-MoS2 can be
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degraded and then excreted almost completely within one month although it does dominate

accumulation in reticuloendothelial systems such as liver and spleen after intravenous injection [15].

Because of the low toxicity and higher peroxidase-like activity, PEG-MoS2 nanosheets should be a

promising material in H2O2 detection. Despite the advantages of using PEG, the cytotoxicity of the

as-exfoliated functionalized nanosheets, of course, still needs to be thoroughly characterized before

translating into clinics.

 Other than the small molecule compounds like H2O2, MoS2 nanosheets and their

functionalized nanocomposites have been also used in the detection of endogenous biopolymers

(e.g., glucose, nucleic acids and proteins), as shown in Table 5. Several MoS2-based

nanocomposites, including PVP-MoS2, SDS-MoS2 and PEG-MoS2, show high detection sensitivity

to glucose [122, 123]. For nucleic acids, MoS2 nanosheets could spontaneously adsorb

single-stranded DNA but it hardly interacted with rigid double-stranded DNA [124]. Bearing this in

mind, a group led by Shuai has constructed a miRNA sensing platform (AuNPs/MoS2) by coupling

hollow MoS2 microcubes with duplex-specific nuclease and enzyme signal amplification [125].

This biosensor is not only practically inactive toward single stranded DNA or

of
single/double-stranded RNA but it also shows an eminent capability to distinguish whether

ro
perfectly matched short duplexes or not. The graphene and CNTs could promote the electron

transfer rate between electroactive species and electrodes for its high electronic conductivity, and
-p
therefore having been used in designing electrochemical sensing platform [50, 53]. Based on this
re
theory, Huang et al. have constructed a functionalized MoS2/MWCNT nanomaterial and

demonstrated that this biosensor could detect DNA down to femtomolar level [49]. The MoS2
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nanomaterials are also applied in the detection of various proteins. For example, a poly

diallyldimethylammonium chloride–graphene/molybdenum disulfide (PDDA–graphene–MoS2)

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nanocomposite with flower-like structure has been constructed for thrombin detection [17].

Analogously, the AuNPs/MoS2 nanocomposite modified electrode also exhibits an excellent

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electrocatalytic activity toward dopamine even in the presence of ascorbic acid [9].
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Table 5 MoS2 nanomaterials used as biosensors for the detection of H2O2 and endogenous biopolymers

f
Nanomaterials Synthesis methods Precursors Reaction conditions Physicochemic Compounds Detection Detection Limit of Reference

oo
al property methods range detection s
(LOD)
MoS2 Ultrasonication Bulk MoS2 and Ultrasonicated for 4 h, Nanosheets H2O2 CV 0.005–100 2.5 nM [12]
and gradient dimethyl gradient centrifuged at μM
centrifugation formamide 1000 rpm for 15 min,
3000 rpm for 15 min

pr
and 6000 rpm for 30
min
MoS2 Solution-based – – Nanosheets H2O2 and UV-vis 5–100 μM, 1.5 and 1.2 [121]
exfoliation glcose absorbance and 5–150 μM,

e-
spectra μM, respectivel
respectivel y
y
SLMoS2 Electrochemical Bulk MoS2 – Fluorgenic DNA (ssDNA Fluorescence 0–15 nM 0.5 nM [124]
lithium-intercalati nanoprobe and dsDNA) spectra

Pr
on
PGE-MoS2 Ultrasonication for (±)-α-Lipoic Ultrasonic for 24 h Nanosheets H2O2 UV-vis 2.86–286 1.18 μM [16]
MoS2 nanosheets; acid-polyethylene with Bulk MoS2 and absorbance μM
Liquid phase glycol (LA-PEG) N,N-dimethylformami spectra
stripping for and bulk MoS2 de
PGE-MoS2 Stirring overnight with
l LA-PEG and MoS2
na
nanosheets
SDS-MoS2 Hydrothermal for (NH4)2MoS4, 200 ℃ for 10 h; Nanocomposite H2O2 and UV–vis 2–100, and 0.32 and [122]
MoS2 nanosheets; N2H4·H2O and Ultrasonic for 48 h glucose absorption 5–500 μM, 0.57 μM,
Ultrasonic for SDS spectra respectivel respectivel
SDS-MoS2 y y
180 ℃ for 12 h 2–150 μM,
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PVP-MoS2 One-pot (NH4)6Mo7O24·4H2 Nanocomposite H2O2 and UV-vis 1.3 and [123]
hydrothermal O and glucose absorbance and 1–10 0.32 μM,
polyvinylpyrrolido spectra μM, respectivel
ne (PVP) respectivel y
y
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MoS2-Pt74Ag26 Hydrothermal Commercial MoS 2, 180 ℃ for 4 h Nanocomposite H2O2 and UV-vis 1–50 μM, 0.4 and 0.8 [126]
nanocomposite polyallylamine glcose absorbance and 1–10 μM,
hydrochloride, spectra μM, respectivel
AgNO3 and respectivel y
H2PtCl6 y
AuNPs/MoS2 Intercalation Bulk MoS2 and 60 ℃ for 5 min Nanocomposite Dopamine CV 0.1–200 80 nM [9]
exfoliation for HAuCl4·3H2O μM
MoS2 nanosheets;
Microwave-assiste
d hydrothermal for
 AuNPs/MoS2
MoS2/rGO/GCE Hydrothermal Na2MoO4·2H2O, 220 ℃ for 24 h Nanocomposite Ascorbic DPV 12–5402 0.72 μM, [50]
NH2CSNH2 and acid, μM, 5–545 0.05 and

f
GO dopamine and μM and 0.46 μM,

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uric acid 25–2745 respectivel
μM, y
respectivel
y
AuNPs@MoS2-QDs One-step Na2MoO4·2H2O, 200 ℃ for 42 h; Nanocomposite Glucose (in UV–vis 20–400 0.068 µM [127]
hydrothermal for L-cysteine and Boiling for 30 min PBS buffer) spectrophotomet µM

pr
MoS2-QDs; HAuCl4·3H2O er
Stirring at boiling
temperature for
AuNPs@MoS2-Q

e-
Ds
PdNPs/PDDA-graphene/Mo Hydrothermal and Na2MoO4·2H2O, 200 ℃ for 24 h Nanocomposite Thrombin CV and DPV 0.001– 0.062 pM [17]
S2 electrostatic PDDA, 5nM
adsorption NH2CSNH2,

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graphene oxide and
K2PdCl4
poly(ChCl-AA Hydrothermal Na2MoO4·2H2O, 200 ℃ for 42 h Nanocomposite β-lactoglobuli High-performanc 100–700 0.7 [117]
DES)@Fe3O4@MoS2 H2NCSNH2, n (in milk) e liquid µg.mL−1 µg.mL−1
FeCl2·4H2O, chromatography
FeCl3·6H2O and (HPLC)
choline
l chloride-acrylic
na
acid (ChCl-AA)
MoS2/MWCNT Hydrothermal Na2MoO4·2H2O, 180 ℃ for 48 h Nanocomposite DNA CV 0.01–1000 0.79 fM [49]
L-cysteine and nM
MWCNTs
AuNPs/MoS2 Hydrothermal HAuCl4·3H2O, 180 ℃ for 24 h Nanocomposite micoRNA CV and DPV 0.1–100 0.086 fM [125]
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MnCO3, MoS2 and fM

L-cysteine
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4.2. Drug delivery and photothermal ablation

Owing to their good biocompatibility, pluggable structures and high near-infrared strong

absorbance, MoS2 as well as their functionalized nanocomposites have also emerged as important

segments to construct nanocarriers in cancer therapy by combining the capability of drug delivery

and photothermal ablation, as shown in Table 6 and Fig. 4. Previous studies have revealed that

Ex-MoS2 acted as an efficient near-infrared photothermal transducer, and can kill tumor cells under

photothermal stimulation [7, 44, 46, 128, 129], and therefore being regard as a promising

light-absorbing nanomaterial for applications in human malignant therapy. On the other hand,

of
functionalization makes high amounts of drug loading on the sheet surface, resulting in effective

therapy of diseases [40]. For instance, the thiolate doxorubicin loaded monolayer MoS2 nanodots

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(DOX-SH/M-MoS2) could serve as a glutathione-responsive nanocarrier for DOX-SH delivery

-p
[130]. Similarly, the functional nano-drugs (ET-MoS2@PEG) can regulate macrophage polarization

and promote anti-inflammatory cytokine expression, thus having been used in immunotherapeutic
re
treatments such as spinal cord injury [18]. MoS2-based biomaterials, however, have emerged only in

the last few years and still remain in their infancy [131]. Therefore, there are many challenges ahead
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toward further clinical applications of MoS2-based nanocomposites in cancer therapy.

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Table 6 MoS2 nanomaterials used in drug/gene delivery and disease treatment

f
Nanomaterials Synthesis Physiochemic Load Objective (in Objective (in Assessment Methods Outcomes Theories Reference

oo
methods al vitro) vivo) endpoints s
characteristics
RGD-QD-MoS2 Lithium Nanosheets – HeLa and Human LDH activity Cytotoxicit RGD-QD-MoS2 Effective [132]
intercalation for HOK cells xenograft Cell apoptosis y and nanosheets show accumulation
SLMoS2; BSA tumormodels Tumor volumes colloidal excellent of
and PEG addition stability fluorescence, RGD-QD-MoS

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and sonication for IR thermal photothermal 2 nanosheets at
RGD-QD-MoS2 camera conversion and the tumor sites
Fluorescenc cancer-targeting through the
e properties RGD-integrin

e-
microscopy targeting
MoS2-ZnO Hydrothermal Nanocomposit – HeLa, Fertilized Cell viability XTT MoS2-ZnO MoS2-ZnO [133]
e HaCaT, chick eggs Expressions RT-qPCR activatescaspase- nanocomposite
A431, xenografts levels of Caspase-3 3, possess
WRL-68 and tumor epithelial and assay down-regulates selective

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HepG2 cells models mesenchymal the expression of cytotoxic
specific genes major activity against
Caspase-3 proangiogenic tumor cells
activity genes (VEGF
and VEGFR2),
and retards the
l process of
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epithelial to
mesenchymal
transition
MoS2-PEG-PEI Chemical Nanosheets Small HepG2 cells – Interfering RT-qPCR MoS2-PEG-PEI MoS2-PEG-PEI [34]
exfoliation for with positive interfering efficiency and WB serves as a exhibits good
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SLMoS2; charge RNA Cell toxicity MTT and nanocarrier for biocompatibilit
Hydrothermal for (siRNA) of FCM efficient siRNA y and reduced
MoS2-PEG-PEI PLK1 gene delivery cytotoxicity
along with high
gene-carrying
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ability
MoS2-PAA and Hydrothermal Nanoflakes – 4T1 and Male ICR In vitro cell CCK-8 and MoS2–PPEG MoS2–PPEG [52]
MoS2-PPEG RAW mice and viability live–dead efficiently kills shows
264.7cells female Tumor volume staining cancer cells in favorable
Balb/c mice and histologic Infrared vitro and photothermal
evaluation of thermal suppresses the performance
tumor-bearing imaging growth of and atractive
mice subcutaneously degradability
xenografted 4T1
tumor in vivo
ET-MoS2@PEG Microwave-assist Self-assemble Etanercept RAW 264.7 Adult female In vitro cell MTT ET-MoS2@PEG ET-MoS2@PE [18]
ed hydrothermal into macrophages C57BL/6J viability Blood obviously G exhibits
nanoflowers and bone mice In vivo toxicity biochemistr inhibits the slower drug

f
marrow stem In vitro cellular y analysis expression of release, higher

oo
cells (BMSC) uptake and Fluorescenc M1-related payloading
anti-inflammato e imaging, pro-inflammator capacity, good
ry activity FCM and y markers but biocompatibilit
The M1/M2 RT-qPCR promoting y, and long
macrophage ELISA M2-related drug
polarization and Cytokine anti-inflammator circulation

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quantitative assays y markers in
inflammatory spinal cord injury
cytokine immunotherapy
analysis

e-
MoS2-CS-DOX Oleum treatment Nanosheets Doxorubici KB and Male Cell mortality CCK-8 Neither MoS2-CS-DOX [128]
exfoliation for n Panc-1 cells BALB/c In vitro In vitro significant cell shows better
SLMoS2; nude mice Biocompatibilit hemolysis mortality nor synergistict
Chitosan (CS) y assay haemolysis of herapeutic

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addition and Tumor-inhibitin In vivo RBCs are effects
sonication for g effectiveness infrared observed in the compared to
MoS2-CS thermal absence of NIR either
imaging irradiation chemotherapy
with DOX or
photothermal
therapy with
l MoS2 alone
na
Fe3O4@MoS2-PEG-2 Hydrothermal Nanocubes Doxorubici L929 and Nude mice Cell viability CCK-8 Efficient Combination of [134]
DG n MDA-MB-23 Cellular uptake Fluorescenc inhibition of phototherapy
1 cells Antitumor e imaging tumor growth and
efficiency Infrared chemotherapy
thermal
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imaging
MoS2-PEG/DOX; Chemical Nanosheet Doxorubici HeLa and KB 4T1 Cell viability MTT MoS2-PEG/DOX Combination of [129]
MoS2-PEG-FA/DOX exfoliation for n cells tumor-bearin CellularDOX fl FCM shows combined phototherapy
SLMoS2; g mice uorescence IR thermal photothermal and and
Hydrothermal for intensities camera chemotherapy chemotherapy
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MoS2-PEG-PEI Temperature both in vitro and

change in vivo
Tumor volume
4.3. Bio-fluorescence imaging

An effective therapy of human diseases including cancer often requires an accurate diagnosis.

To realize personalized medicine, optimize therapeutic efficiency and monitor therapeutic responses,

the bio-fluorescence imaging before, during, and after therapy has been playing increasingly vital

roles in guiding the planning of treatment for individual patients [135, 136]. Due to their tunable

large band-gaps, strong exciton and fluorescence properties, 2D-TMDs (e.g., MoS2, WS2, and

g-C3N4) were considered as candidates for potential bio-imaging and diagnosis [40, 135]. Those

MoS2 nanosheets particularly have been used as a promising contrast agent in X-ray computed

of
tomography imaging because of their obvious X-ray absorption ability of Mo [128]. Organic

fluorophores have been intensively used for detecting specific biomolecules and imaging biological

ro
microenvironments, such as pH, viscosity and temperature [130, 137]. Based on these theories,

-p
MoS2-based nanocomposites with other functional nanostructures could be explored in cancer

diagnosis.
re
Fig. 4 MoS2 nanomaterials used in combined photothermal and chemotherapy of cancer

5. Health risks assessment of MoS2 nanomaterials

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Since a large number of nano-products based on MoS2 nanomaterials have being used in

environmental and biomedical applications, their safety with regard to the environment and
na

organisms has attracted considerable attention. Importantly, determination of their potential risks is

of fundamental importance for the translation of them into use. To understand the suitability of
ur

MoS2 nanomaterials in environmental and biomedical applications, the toxicities of them have been
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assessed with various toxicological endpoints using different experimental protocols (e.g., in vitro

and in vivo models), as summarized in Table 7–8. The ability of nano-MoS2 to enter cells and affect

their biochemical function makes them as vital tools at the molecular level. MoS2-induced cytotoxic

responses, of course, depend on the dose and compositions of MoS2 nanomaterials themselves, the

selected research models as well as assessment assays. Specifically, nano-MoS2 synthesized by

different methods would exhibit noticeably different biological effects. The toxicology overview on
the principal components of MoS2 nanomaterials is illustrated in Fig. 5. Overall, several in vitro and

in vivo models were adopted currently to assess the toxic effects of MoS2 nanomaterials on various

endpoints. However, the risk assessment results can be affected by several influence factors,

including MoS2' physicochemical properties, assessment models and methods, and exposure

conditions. To this end, the potential risks on human health and ecosystem stability should be

investigated in future studies.

Fig. 5 An overview on the principal components of MoS2-based nanomaterials' toxicity

5.1. Toxicology assessment with different models

of
Similar to other 2D nanomaterials, MoS2 may also elicit adverse responses to prokaryotic or

bacterial cells as well as eukaryotic mammalian cells. These potential negative effects were

ro
assessed in laboratory environments with numerous in vitro and in vivo models.

5.1.1. In vitro models -p

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The cytotoxicity of MoS2 has been investigated using different in vitro cell models and

incubation times/doses. It is clear that different types of MoS2 did induce cytotoxicity, as shown in
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Table 7. Several endpoints were analyzed to assess the cytotoxicity of MoS 2, including cell viability,

membrane integrity, ROS production, lipid peroxidation and apoptosis. Presently, the cell viability
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is one of the most used assessment endpoints which is based on several colorimetric assays,

including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT),

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3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxym-etho-xymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetraz

olium dye-reduction assay (MTS), cell counting kit-8 assay (CCK-8) and
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2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium assay

(WST-8). However, these colorimetric assays may lack reproducibility due to the interference of

nanomaterials [138]. The in vitro dispersion and protein corona effects would affect the validity and

reproducibility of toxicological outcomes [139]. Hence, several more extensive and elaborate

toxicity screening assessment techniques, including the flow cytometry (FCM), high content

screening (HCS) and live/dead viability assay [18, 22, 132], are gradually adopted to accurately
identify and confirm the cytotoxicity induced by nano-MoS2. Moreover, the changes in DNA

structure and gene expression levels induced by oxidative stress are interesting approaches to

monitoring the nanotoxicity of MoS2 nanomaterials.

Generally, the cytotoxicity of MoS2 nanomaterials depends on the physiochemical properties

of nanomaterials themselves especially layers and complex, the exposure time and doses, and the

used in vitro models. By using the wild-type and endotoxin hypo-responsive bone marrow derived

dendritic cells (THP-1) as an in vitro model, Moore et al. confirm that the inflammatory responses

result from a combination of endotoxin contamination, the MoS2 nanomaterials themselves, and the

stabilizing surfactant [22]. Different from other nanomaterials (e.g., nano-ZnO and nano-TiO2)

of
which show higher cytotoxicity in mammalian cells [140], the 2D-MoS2 as well as Ex-MoS2 exert

ro
lower cytotoxicity. However, they still significantly inhibit the growth of some tumor cells at

high-doses exposure [7, 44]. Importantly, decreasing the number of layers of 2D-MoS2 would
-p
increase the toxicity in several mammalian cell lines [7, 32, 33, 44]. As an example, SLMoS2
re
induces strong proinflammatory and profibrogenic responses to the THP-1 and BEAS-2B cell lines

than that of 2D MoS2, such as PF87-MoS2 and Lithiation-MoS2 [8]. Other study also revealed that
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the cytotoxicity is in order of MoS2/PEG < MoS2 < MoS2/PEG-PEI on HeLa cells in dose- and

time-dependent manners [34]. Similarly, MoS2-TBA has become less toxic as compared to MoS2
na

[7]. These studies all suggest that MoS2-induced cytotoxic responses are dependent on the dose and

composition of MoS2 nanomaterials themselves. Indeed, the exposure doses used in nanotoxicology
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research sometimes are so high that they have no real world relevance, leading to questionable

assessment results.
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Other than the different types of nano-MoS2 materials themselves, the choice of different in

vitro models, however, can also bring about disparate evaluation results. The Ex-MoS2 has been

found inducing antiproliferative effects in some in vitro tumor models, such as A549, HeLa and

MCF-7 cells [7, 16, 34]. In contrast, Ex-MoS2 exerts very low cytotoxicity in NIH/3T3 fibroblast

cells up to 100 µg.mL−1 [32]. It should be noted that the NIH/3T3 cells were exposed to low
concentrations of MoS2 nanosheets and for only 3 h processing period before MTS viability

analysis. Though 3 h exposure time may not be enough to reflect the long-term effects, and the

concentration selected were non-toxic, the use of MTS assay might also overestimate the

non-toxicity results. Similar results have been found by Appel and co-workers [103]. Compared

with the Ex-MoS2, 2D nano-MoS2 nanosheets are biocompatible towards HEK293f and don't

trigger the generation of high levels of ROS that accompanies cell death [103]. Similarly,

MoS2/PEG and MoS2/PEG-PEI nanocomposites show no toxicity even at the highest concentration

of 200 µg.mL−1 in MCF-7, HepG2, HeLa and 293T cells although they do induce cytotoxicity in

HeLa cells [16, 34]. However, raw 2D MoS2 still exerts higher antibacterial activity on Escherichia

of
coli [110], suggesting different toxic effects induced by MoS2 are associated to the different

ro
organisms tested. To avoid false results, the extremely careful and systematic investigations,

therefore, must be undertaken to determine the appropriate assays, conditions and handling.
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Table 7 In vitro studies of toxicology by typical MoS2 nanomaterials

f
Nanomaterials In vitro models Assessment endpoints Methods Doses Timing Outcomes References
3.125−400

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Ex-MoS2 A549 Cell viability MTT and 24 h MoS2 nanosheets [44]
WST-8 µg.mL−1 exfoliated with t-Bu-Li and
n-Bu-Li are significantly
cytotoxic than Me-Li
exfoliated nanosheets
Ex-MoS2, MoS2/TBA A549 Cell viability MTT and 0−100 µg.mL−1 24 h MoS2/TBA has less toxicity [7]

pr
WST-8 than that of MoS2
MoS2 nanosheets THP-1, A549 and human Cell viability High content 0−10 µg.mL−1 24 h MoS2 nanoflakes of three [22]
gastric adenocarcinoma screening, sizes at a concentration of 1
cells live/dead µg.mL−1 are non-toxic

e-
viability assay
SLMoS2 (Ex-MoS2 and Fibroblast NIH/3T3 cell Cell viability MTS 50 and 100 3h Ex-MoS2 presentes no [32]
Ae-MoS2) µg.mL−1, mortality but Ae-MoS2
respectively presentes a mortality of
18%

Pr
Aggregated-MoS2 THP-1 and BEAS-2B Cell viability and MTT and 6.25−50 µg.mL−1 24 h Aggregated-MoS2 induces [8]
Lithiation-MoS2 anti-inflammatory ELISA strong proinflammatory
PF87-MoS2 cytokine (IL-8, TNFα and profibrogenic
and IL-1β) responses than PF87-MoS2
and Lithiation-MoS2
MoS2 HepG2 Cell viability, ROS CCK-8, FCM, 0−30 µg.mL−1 24 h MoS2 (Commercial [141]
l generation, membrane LDH release sources) significantly
na
damage and and RT-qPCR reduces cell viability at 30
Anti-inflammatory gene µg.mL−1
expression
MoS2, MoS2/PEG, HepG2, HeLa and 293T Cell viability MTT 200 µg.mL−1 24 h No significant cytotoxicity [34]
MoS2/PEG-PEI but different sensitivities
ur

are found in three in vitro

models
MoS2 (2D nanosheets) HEK293f Cellular morphology and SEM, live/dead 0.1, 1 and 10 4, 12, 24 2D sheets MoS2 is [103]
cell apoptosis viability assay µg.mL−1 and 48 h biocompatible towards
and ROS HEK293f and doesn't
Jo

generation trigger the generation of

high levels of ROS that
accompanies cell death
PVP-MoS2 HeLa and BEL-7402; Cell viability and CCK-8 and 0−200 µg.mL−1 24 h PVP-MoS2 exerts low [123]
red blood cells (RBCs) biocompatibility hemolysis assay cytotoxicity on HeLa and
BEL-7402 cells up to 200
µg.mL−1, but it shows good
biocompatibility on RBCs
MoS2, MoS2/PEG Breast cancer cell lines Cell viability MTT 0−200 µg.mL−1 24 h MoS2/PEG shows no [16]
significant toxicity on
 breast cancer cells even up
to 200 µg.mL−1
MoS2, MoS2/PEG HeLa Cell viability and ROS MTT and FCM 0−160 µg.mL−1 24, 48 and The cell viability is [129]

f
generation 72 h moderately reduced by

oo
MoS2, whereas no
significant effect is
observed for MoS 2/PEG
even at high concentrations
of 160 µg.mL−1
nisin@PEGylated MoS 2 HeLa Cell viability CCK-8 0−50 µg.mL−1 24 h The conjugate shows very [11]

pr
low toxicity towards HeLa
cells whereas the cell
viability decreases slightly
with the increase of

e-
expousre concentrations

l Pr
na
ur
Jo
5.1.2. In vivo models

To our best knowledge, despite a few studies have investigated the interactions of MoS2

nanomaterials with microorganisms, algae and invertebrates, there still spare researches have been

conducted on vertebrates. Herein, TiS2-PEG, another typical 2D-TMD, exerts excellent

photothermal therapy efficiency on mice 4T1 tumors under nearinfrared (NIR)-laser irradiation

[142]. Considering that TMDs have their different compositions, the in vivo studies on MoS2 are

still necessary. By using the modern tools of toxicological pathway identification, we can compare

the effects of various MoS2 nanocomposites to each other and try to rank them related to specific

of
adverse outcome pathways. Some typical in vivo studies about the MoS2 nanomaterials and their

ro
potential mechanisms as well are shown in Table 8. In general, the MoS2 nanosheets induce

toxicology more or less in different in vivo models, while surface functionalization of them would
-p
decrease the potential toxicity. Recently, the application of advanced cell culture techniques such as

the 3D cell culture has brought more realism into the classical cell culture systems, further
re
improving their relevance for toxicity screening and testing of objective compounds without the use
lP

of animals [143]. Such technique could be used to assess the potential toxicity of nanomaterials

more convincing.

As for human health risks, the toxic effects of usual nanomaterials are outlined based on the
na

type of body compartment, including reproductive, respiratory, dermal, hepatic, renal,

cardiovascular, immune and neural system. The available toxicity studies mainly focused on effects
ur

after nanomaterials exposure via respiratory inhalation, skin exposure, food additive ingestion, and
Jo

nano-therapeutics [144]. Among these exposure routes, inhalation exposure might contributes the

highest risks since MoS2 nanomaterials are processed as unique powders with plate-like structure,

atomic thinness and extreme aspect ratio, as introduced in Section 2.2. To our best knowledge, there

is limited existing research regarding clinical implications of MoS2 nanomaterials, though their

roles in some animal models have been studied. Presently, carcinogenicity and occupational

exposure risks have been ordinarily assessed using high doses.

Table 8 In vivo studies of toxicology by typical MoS2 nanomaterials

f
Assessment
Nanomaterials Species Route Organs Methods Doses Timing Outcomes Mechanisms References

oo
endpoints
Agg-MoS2
Pluronic coating
induces acute
of MoS2 sheets
inflammation in
Neutrophil cell increase the
Aggregated-MoS2 the lungs of
counts, Immumohistochemical dispersibility and
Lithiation-MoS2 Mice Ingestion Lungs 2 mg.kg−1 40 h mice, whereas [8]

pr
proinflammatory staining biocompatibility
PF87-MoS2 PF87- and
cytokine of MoS2 by
Lit-MoS2 have
reducing the
no effects on
surface reactivity
inflammation

e-
SLMoS2 is Cellular
Cell growth,
clearly internalization of
chlorophyll, cell
cytotoxic to the
permeability,
Chlorella nanomaterials;
mitochondrial Flow cytometry and 10, 100
SLMoS2 and Alage (Chlorella vulgaris, Shrinkage of the

Pr
– – membrane UV−vis and 1000 24–96 h [21]
SLMoS2−HA vulgaris) whereas the plasma membrane
potential, spectrophotometer µg.mL−1
cytotoxicity of or plasmolysis;
glutathione
hybridized Inhibition of
content and ROS
SLMoS2−HA is chlorophyll
generation
negligible biosynthesis
Microcrustacean 10−100 24 and No signifcant
–
2D-MoS2
(Artemia salina) l
Ingestion Larvae Mortality Dead- motionless count
µg.mL−1 48 h toxicology
[45]
na
SLMoS2 shows
5.7 times higher
than that of
annealed
SLMoS2 (Ex-MoS2 10–200 1 and 3 exfoliated MoS 2
Planktonic Ingestion Plank Survival rate Plate count – [32]
µg.mL−1
ur

and Ae-MoS2) h against

planktonic cells
in the presence
of 40 mg.L−1
EDTA
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Dissolved oxygen
Dissolved
Algal division, and visible light
oxygen and
cellular irradiation
visible light
ultrastructure significantly
1, 10 and irradiation drive
Alage (Chlorella observation, FCM count, TEM, 24, 48 accelerate the
SLMoS2 – – 25 the structural [14]
vulgaris) nanomaterial ICP-MS and GC-MS and 72 h chemical
µg.mL−1 alterations and
uptake, ROS dissolution of
phytotoxicity
generation and SLMoS2 to
mitigation of
algal metabolism 1T-phase and
SLMoS2
2H-phase
 SLMoS2, while
the 2H−phase
SLMoS2 could

f
not easily enter

oo
algal cells
No significant
toxicity even at
Alage (Chlorella 0–200
MoS2/PEG – – Cell viability Colorimetry 24 h high – [16]
vulgaris) µg.mL−1
concentrations
(200 µg.mL−1)

pr
MoS2
Feeding rate, cell
Behavioral assay, BrdU nanoparticles
proliferation, cell
Asian labeling assay, AO/EB induce cellular
apoptosis, Behavioral
weaver ant staining, FCM, 10–100 toxicity in the
–

e-
MoS2 Ingestion oxidative stress, 24 h alteration and [112]
(Oecophylla fluorescence µg.mL−1 foragers of the
lipid peroxidation oxidative stress
smaragdina) microscopy staining and weaver ant
and antioxidant
colorimetry (LC50=50
enzyme activity
µg.mL−1)

l Pr
na
ur
Jo
5.1.3. Correlation between in vitro and in vivo studies

Correlation between in vitro and in vivo effects is an indication that specific cells, tissues or

organisms are potential targets for MoS2 toxicity. For instance, although in vitro and in vivo studies

have demonstrated that MoS2 can induce adverse effects, several in vitro studies show that MoS2

caused DNA double-strand breaks in a wide range of immortalized cell lines at relative low doses

while no such genotoxic effects are observed even at high doses in animals [16]. Moreover, MoS2'

toxicity remains less well established mainly due to the improper-unrealistic-dosing both in vitro

and in vivo. Small differences in the physicochemical properties of MoS2 that functionalized by

of
some small molecules, of course, could contribute to significant variation in the toxicity, as shown

ro
in Table 7–8. According to recent publications, there are still many gaps in available experimental

data devoted to risks assessment of MoS2 nanomaterials although several in vitro and in vivo
-p
protocols have been studied. Therefore, more attention must be given to appropriate MoS2' risks.

5.2. Toxicology mechanisms involved in MoS2 nanomaterials exposure

re
MoS2 induced toxicity via manners similar to other nanomaterials. Particle size, morphology,
lP

composition and surface characteristics (e.g., layer number, lateral dimension, crystal structure and

colloidal stability) are important parameters that reflecting the toxic effects of nanomaterials [25,
na

103, 145]. Generally, the smaller the particle diameter, the higher the surface energy and the

stronger the surface-atoms activity would be generated, thus inducing stronger toxicity. By using
ur

the HEK293f model, Osman et al. have shown that materials larger than 100 nm in diameter will

not undergo endocytosis [146]. In contrast, nanomaterials can translocate from the entry portals (i.e.,
Jo

skin, lungs and gastrointestinal) into the circulatory and lymphatic systems, and ultimately to body

tissues and organs [144]. That is why the toxicity of nanoparticles is significantly higher than that of

conventional particles at the same concentrations. For MoS2 nanomaterials, the more exfoliated the

MoS2 nanosheets, the stronger their cytotoxic influence [5, 8, 32, 108], which may be dependent on

an increase in surface area and active edge sites. MoS2 nanomaterials are supposed to exert their

toxic effects via a direct oxidative stress manner or an indirect non-oxidative stress manner, as
illustrated in Fig. 6. Compared to the oxidative stress manner, cytotoxic effects induced by MoS2

nanomaterials in the absence of oxidative stress are relatively scarce. The crosstalk between

oxidative stress manner and the non-oxidative are also involved.

5.2.1. Toxicological effects associated with oxidative stress

Generally, photoactive nanomaterials including MoS2 can react with oxygen or strong

oxidizing agents to produce ROS under the conditions of visible light irradiation [14], as shown in

Fig. 6A These intracellular ROS would induce oxidative stress, broke the balance towards

intracellular ion homeostasis (i.e., Ca2+ and K+) and increased membrane permeability [118, 147,

of
148]. Actually, nanomaterials induce oxidative stress and mediate apoptosis mainly via the intrinsic

ro
or mitochondrial pathway (caspase-dependent pathway) with a size- and dose-dependent manner

[103]. Among these manners, ROS-mediated toxicity has been believed to be an important
-p
mechanism of nanomaterials' toxicity [31, 80, 141, 149]. Oxidative stress is defined as an imbalance

between the production of ROS and antioxidant defenses in the body [150]. The intracellular
re
protective enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione
lP

peroxidase (GSH-Px) can remove ROS, ultimately minimizing damage [149]. In contrast, excessive

production of ROS can induce oxidative damage of important cellular molecules (i.e., lipids,

proteins and DNA), ultimately leading to cell growth inhibition or even apoptosis [151]. Several
na

studies have found that SLMoS2 nanosheets are more toxic than their multilayer or bulk

counterparts [8, 110], suggesting that diameter or size plays a vital role in toxicity. Moreover,
ur

Ex-MoS2 nanosheets are certified to generate more ROS owing to their higher electron conductivity
Jo

than that of bulk MoS2, resulting in enhanced cytotoxicity on multiple exposure objectives [32, 58,

108].

The excessive ROS has been found to inhibit adenosine triphosphate (ATP) production and

reduce mitochondrial membrane potential [8, 139, 152]. Such ATP depletion would then inhibit

DNA replication and glutathione biosynthesis [152], eventually inhibits cell proliferation.

Meanwhile, the loss of mitochondrial membrane potential, of course, also induces intracellular
components release (e.g., lactic dehydrogenase (LDH) and cytochromes) and activates apoptotic

and pro-inflammatory signaling pathways along with gene expression [8, 18, 141]. The increased

release of LDH and cytochromes in return would reduce the membrane stability and organism's

resistance to external conditions [108], finally promoting apoptosis and necrosis. These theories

associated with oxidative stress are indicated in Fig. 6C1.

5.2.2. Toxicological effects not associated with oxidative stress

Nevertheless, MoS2 can also cause cytotoxicity without measurable levels of ROS production

but the disturbance of membrane integrity due to direct cell-nanomaterial interaction [11, 117].

of
Generally, the MoS2 complex materials firstly adsorb on the cell surface through passive uptake or

ro
physiochemical interactions that initiated by van der Waals forces, electrostatic charges, steric

interactions or interfacial tension effects. MoS2 can also interact with membrane proteins by binding
-p
to K+ channels [148]. And then, the nanomaterials would penetrate the cell membrane or cytoderm

to interact with subcellular structures or biomolecules (Fig. 6B1). Such cellular internalization of
re
nano-MoS2 generally involves in cell shrunk, plasmolysis and membrane permeability increment
lP

[21]. Moreover, adsorption of nanomaterials on cell surface leads to membrane/wall depolarization

[108] and then changes their typically negative charge to become more permeable [34, 48], as

shown in Fig. 6B2. As a result, constituents will be released when the cytoplasmic membrane is
na

disrupted, consequently leading to cell death.

The internalized nano-MoS2 nanomaterials would inhibit the synthesis of biomacromolecules

ur

(i.e., carbohydrates, lipids, proteins and DNA) or oxidative damage these biomacromolecules (Fig.
Jo

6C2). In addition, they may also induce proinflammatory effects, and then modulates intracellular

Ca2+ concentration, thereby activating transcription factors to control cell apoptosis (Fig. 6C3).

MoS2 internalization, of course, is always accompanied by both cellular metabolic disorders and

oxidative stress [141, 153]. For instance, SLMoS2 nanosheets could reduce the levels of fatty acids,

urea, amino acids, and other small molecule acids in Chlorella vulgaris [21], resulting in

deterioration of membrane fluidity and osmotic stress.

Fig. 6 Schematics of the molecular events by which MoS2 nanomaterials exert their toxic

effects

(A) MoS2 nanomaterials react with oxygen or strong oxidizing agents to produce ROS under the conditions of
visible light irradiation. MoS2 nanomaterials penetrate the cell membrane or cytoderm in direct way (B1) and
indirect way (B2) to interact with subcellular structures. MoS2 nanomaterials exert toxicity via oxidative stress
(C1), biomacromolecules inhibition and damage (C2), and inflammatory response (C3).

6. The tradeoff between applications and risks

As summarized in Section 2-4, MoS2 and MoS2-based nanomaterials with diverse phases (e.g.,

1T-phase, 2H-phase and 3R-phase) have different physiochemical characteristics, and thus exert

of
different properties in various fields. Moreover, the surrounding environmental conditions (i.e., pH,

oxygen and light irradiation), of course, would also influence their geometry, aggregation behavior

ro
and solubility, ultimately generating great difference in their environmental and biomedical

-p
applications. Therefore, both internal (physiochemical properties) and external factors (surrounding

environmental conditions) would restrict the potential applications of MoS2 nanomaterials. Bearing
re
this in mind, advanced analysis of the changes of MoS2 nanomaterials' physicochemical

characteristics, therefore, will continue to be essential. To obtain accurate description of each

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physicochemical characterization endpoint of MoS2 nanomaterials, more than one appropriate

technique for physicochemical characterization should be employed in specific applied scenarios

na

before, during and after the application process. These physicochemical characterization endpoints

include primary particle size distribution, layers, phases, hydrodynamic diameter, volume specific
ur

surface area, agglomeration behavior, surface reactivity and dissolution kinetics.

Jo

There would be several potential risks, of course, in the application processes of MoS2

nanomaterials. Compared with their positive applications, possible undesirable results of MoS2

nanomaterials are their harmful interactions with biological systems or eco-environment. Exploring

the balance between applications and risks, therefore, is vital in MoS2 nanomaterials' large-scale

application, as shown in Fig. 7. Importantly, developing highly effective MoS2 nanocomposites

along with an early-stage research on their implications of environmental health and safety should
be essential tasks now and in the future.

6.1. The MoS2-induced cytotoxicity can be used in therapeutic and aseptic

applications

Although the potential toxicity of MoS2 nanomaterials are still an in vitro and in vivo

exploration (Section 5.1), they do impact on the cellular uptake, cytotoxicity and inflammation

especially under the conditions of light irradiation [14, 22, 142]. The toxic properties of MoS2

nanomaterials can, in some instances, be applied to improve human health through targeting cancer

cells or harmful bacteria and viruses, as concluded in Section 3.3 and 4.2. Those anticancer or

of
antibacterial effects are closely associated with the ROS-mediated oxidative stress. Importantly,

MoS2 nanomaterials especially the functionalized ones loaded with other drugs result in effective

ro
action on diseases therapy and sterilization. For instance, several functionalized MoS2
-p
nanocomposites can efficiently kill various cancer cells in vitro as well as suppress the growth of

subcutaneously xenografted tumor in vivo [52, 129, 132]. In addition, numerous studies have
re
reported the bacterial toxicity of MoS2 nanomaterials [31, 32, 68], and thus may be applied in
lP

antimicrobial products.

In contrast, MoS2 nanosheets those are not capable to penetrate or cut the cell membrane to

induce stress to cause cell death [154], have been considered as potential candidates for biological
na

applications such as gene transfection and bio-imaging (Section 4). Moreover, the 2D MoS2

nanomaterials exert distinct optical and electronic properties but low toxicity than that of the
ur

aggregated MoS2, making them widely used in electronic and biomedical sensors [8, 22]. The MoS2
Jo

nanocomposites, such as MoS2-PEG, MoS2-PEI and MoS2-PPEG, exert no appreciable cytotoxicity

on several in vitro cell models without photothermal treatment [16, 34, 52, 129]. Importantly, they

show attractive degradability under physiological conditions (pH 7.4) than that of acidic condition

(pH 5.0) [52]. As mentioned above, we can appropriately use different types of MoS2 nanomaterials

on different environmental and biomedical occasions following a correct distinguish of their

potential toxicity. It cannot be denied, of course, that though MoS2 nanomaterials may be dangerous
for the environment and human health, they can also be explored for therapeutic applications such

as anticancer therapy and antibacterial agents. Besides, some newly synthesized MoS2

nanomaterials, of course, potentially have excellent performances in other unexplored applications,

identifying the most suitable application for each MoS2-based nanocomposite is important in future

research.

6.2. Environmental and biomedical applications of MoS2 nanomaterials

may generate secondary negative-effects

MoS2 nanomaterials have been widely used in environmental and biomedical applications, as

of
mentioned in Section 3 and 4. However, such exploited benefits might generate secondary negative

effects on the environment and human health. As is known to all, nanomaterials including MoS2

ro
that used in the detection and removal of environmental contaminates might also exert negative
-p
influence on the environmental organisms, such as bacteria, algae, protozoa and aquatic animals

[144], as shown in Fig. 7. Specifically, MoS2 nanomaterials would be inevitably exposed to sunlight
re
or artificial light source after released into environmental media [32], resulting in prominently
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increase of ROS and potential toxicity on environmental organisms.

First, different organisms sometimes show different responses to MoS2 nanomaterials. As an

example, Fu and co-workers [117] recently have synthesized a novel choline chloride-acrylic acid
na

deep eutectic solvent polymer based on Fe3O4-particles and MoS2-nanosheets [poly (ChCl-AA DES)

@Fe3O4@MoS2]. Such MoS2-based nanocomposite not only exhibits specific recognition of

ur

bio-macromolecules (β-lactoglobulin), but also has better antimicrobial effects against common
Jo

bacteria (i.e., Escherichia coli, Staphylococcus aureus and Bacillus subtilis), and thus considering

as an ideal carrier for bio-macromolecules in real samples [117]. Unfortunately, it could slightly

promote the growth of another gram-positive bacterium (Pseudomonas fluorescens) [117]. Since the

poly (ChCl-AA DES)@Fe3O4@MoS2 nanomaterials only exert obvious antibacterial effects against

some bacteria, they could be applied in some but not all areas. In other words, we should consider

the actual situation before selectively using different functionalized MoS2 nanomaterials.
 Second, MoS2 and its functionalized MoS2-nanocomposites that used as biosensors for

endogenous compounds detection (e.g., ROS, glucose, proteins and nucleic acids) usually exert low

cytotoxicity. Indeed, those nanomaterials may also have potential risks despite they actually only

exert low cytotoxicity, and thus limit their application and promotion. Similarly, nano-MoS2

nanomaterials used to kill tumor cells (Section 4.2 and 4.3) may cause potential adverse effects

elsewhere in human body. Previous studies have demonstrated that SLMoS2 nanosheets induced

stronger proinflammatory and profibrogenic responses to human cancer cell lines [8] and higher

antimicrobial ability [32] compared with the bulk ones. Unfortunately, these SLMoS2 nanosheets

have greater potential to be quickly released into the environment during their fabrication, transport,

of
storage, use and disposal [21]. So, what will happen when other normal organisms or cells were

ro
exposed to such nanomaterials either deliberately or inadvertently?

At last, the different exposure duration and concentrations actually often resulted in different
-p
toxic effects. Some researchers used very high concentrations that may cause “overloading” of cells
re
and modify the nature of nanomaterials–cell interactions since the environmental concentrations of

nano-MoS2 are at relatively low levels [14]. Moreover, there is no clear commitment about what
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minimum requirements are necessary to establish a reference material which can be used to validate

and compare toxicology methods [155]. In those cases, it is difficult to evaluate whether the
na

observed effects were physiologically relevant. Bearing this in mind, a better physicochemical

characterization of functionalized MoS2 nanomaterials has emerged as a crucial aspect for reliable
ur

assessments of the potential risks in their actual use. Through which we can verify the relationship

between their properties (e.g., morphology, size, and composition) and behaviors (e.g., reactivity,
Jo

aggregation, and kinetics) [144]. Studies on kinetics and biochemical interactions of nano-MoS2

with exposure objectives, of course, are imperative. Specifically, their surface functionalization

characteristics, the migration and transformation pathways, long- and short-term toxicity, their

interactions with cells through different signaling pathways must be explored in future.
6.3 Other concerns

The synthetic methods (e.g., hydrothermal and exfoliation), application forms (e.g., dry

powder or suspension spiking), exposure roots (e.g., water, soil and sediment) sometimes affect the

extent of nanomaterials' bioavailability [1], ultimately exhibit noticeably different biological effects.

Compared to the pristine nanomaterials, environmentally-transformed nanomaterials may exhibit

different morphologies, structures, and stabilities, leading to alterations of their ecological and

health effects [14]. Particularly, several environmental factors, including pH, ionic strength,

dissolved oxygen, light irradiation and natural organic matters (NOM), show greater influence on

of
the transport and transformation of MoS2 nanomaterials by changing their physiochemical

properties and environmental stability, ultimately affects their potential health risks [5, 14, 21]. For

ro
example, HA over 10 mg/L can change the structure and dispersion of single-layer MoS2, and

-p
thereby reducing the toxic effect of MoS2 on algal [21]. Presently, although several methods are

reasonably well-established to assess most required properties for pristine (as-produced)

re
nanomaterials including MoS2, they are frequently applied in different ways and are not always

sensitive to environmental and/or working conditions [156]. Actually, physicochemical properties of

lP

nanomaterials are interdependent for their potential nanotoxicity. Mastering the aggregation

behaviors such as physicochemical property changes and environmental stability of MoS2

na

nanomaterials, therefore, is crucial for their environmental implications and ecotoxicological studies.

Acturally, environmentally transformed MoS2 nanomaterials, apart from the pristine ones, should
ur

deserve much attention to guarantee their environmental safety.

Fig. 7 The stable balance between applications and risks of MoS2 nanomaterials
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7. Establishment of a comprehensive evaluation system used in MoS2

nanomaterials' potential risks

The cytotoxicity of MoS2 nanomaterials has been investigated using some different in vitro and

in vivo models, as summarized in Section 5.1. Nevertheless, the toxicology field of MoS2
nanomaterials is too young and the literature is too limited to reach conclusions about potential

hazards sufficient for risks assessment or regulation. Moreover, their environmental risks and

human health have been evaluated much less compared to other nanomaterials within the last

decade. As a result, there are still many knowledge gaps between nano-MoS2 and other

nanomaterials. Presently, most data on the biological effects of MoS2 nanomaterials are obtained

from traditional cytotoxicity or fewer ecotoxicity testing (Table 7 & 8). Different models were

incubated with different types of MoS2 nanomaterials at different times and doses, making the

comparison between studies difficult. Indeed, the development of methods to evaluate the safe use

of MoS2 nanomaterials and their potential risks has not kept pace with their rapid commercialization.

of
Specifically, the lack of adequate detection and characterization techniques and lack of reproducible

ro
and validated methods for toxicological studies have been identified as major bottlenecks for the

safe and sustainable use of nanomaterials, as previously reviewed [156, 157]. It is urgent and
-p
necessary to establish more comprehensive and accurate assessment systems to evaluate the
re
potential risks of different MoS2-based nanomaterials. Although several studies have been

conducted in assessing the potential toxicity of MoS2 nanomaterials, there are still several critical
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points should be emphasized and improved.

Firstly, the physicochemical properties of MoS2 nanomaterials play vital roles in their toxic
na

effects. Unfortunately, traditional instrument analysis methods cannot effectively determined the

physiochemical properties of MoS2 nanomaterials due to their lower concentrations used in

ur

toxicology field. Thus, an adequate characterization of MoS2 nanomaterials is necessary to found

the relationship between potential risks and MoS2 nanomaterials' physicochemical properties.
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Secondly, the physicochemical properties of MoS2 nanomaterials are complicated and diverse.

Those properties include intrinsic properties (e.g., size, layer number, lateral dimension, surface

area and composition) and extrinsic properties (e.g., surface charge, surface chemistry and

aggregation). It is commonly recognized that the lateral size is a key variable in cell uptake for

MoS2 nanomaterials, while layer number can affect the deposition, surface area and surface
chemistry, ultimately affect their adsorption and dispersibility. Indeed, MoS2 nanomaterials can be

synthesized in many different variants by varying size, layer, and crystal phase or by applying

chemical surface modifications, as shown in Section 2.2. On the other hand, the experimental

medium or simulated environment would often change the extrinsic properties of MoS2

nanomaterials, and then determine their fate, reactivity and bioavailability. As a result,

complexation to or adsorption of matrix components such as NOM and the aggregation or

sedimentation of the MoS2 nanomaterials can dramatically change their transport and bioavailability.

Therefore, the combined effects of coexisted factors in matrix environment should be taken into

consideration when evaluated the potential toxicities of MoS2 nanomaterials.

of
Thirdly, it is acknowledged with a higher level of urgency to systematically address in vitro

ro
dispersion, protein corona effects, and their impacts on the validity and reproducibility of

toxicological outcomes in both internal and external environment (i.e., exposure medium and
-p
biological fluids within the organisms). Additional, two important methodologies, namely
re
short-term inhalation study with cellular assays and long-term multi-generation experiments with

environmental relevant organisms, should be carried out simultaneously to make better estimates of
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the risks of MoS2 nanomaterials. The former often use target cells to assess the potential of MoS2

nanomaterials to cause acute toxicity and inflammation, whereas the latter employ models
na

organisms (e.g., mice, rat, rabbit, fishes, algae and protozoa) to assess the biodistribution,

bioaccumulation, biopersistence and chronic toxicity induced by MoS2 nanomaterials (Fig. 7).
ur

Long-term adverse health impacts, of course, must be considered in the design of MoS2

nanomaterials for fluorescence-based biomolecular sensing and drug delivery. Broadly applicable
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studies in both in vitro and in vivo studies are also resurfaced with more urgency since the dose

ranges used in nanotoxicology research are continue to be high, sometimes so high that they have

no real world relevance. Based on the knowledge about the doses, relationships between the

material itself and the effective dose can be established.

Lastly, the interactions between different coexisted environmental contaminants (i.e., EDCs,
antibiotics and heavy metals) with MoS2 nanomaterials in different assessment models following

mixture exposure need systematically studied. Actually, an unexpected toxic effect would be

generated when simultaneously exposed to a mixture of MoS2 nanomaterials and other different

environmental contaminants.

8. Conclusions and perspectives

In the present review, we have outlined the recent progress in the synthesis, applications and

potential health risks of the emerging MoS2-based nanomaterials. Overall, MoS2 nanomaterials as

well as their functionalized ones have been widely manufactured with different synthetic methods

of
as required and applied in environmental protection and biomedical fields due to their excellent

physicochemical properties. In environmental protection field, MoS2 and MoS2-based

ro
nanocomposites have been used in the detection of the pollution levels of different conventional and

-p
trace contaminants. Moreover, they have been also applied in environmental pollution cleanup

through physical mode (i.e., adsorption and membrane filtration) or chemical mode especially
re
photocatalysis. MoS2 nanomaterials, of course, are also used as antibacterial agents to devitalize or

even kill the pathogenic bacteria. As for biomedical applications, MoS2 nanomaterials have been
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used as biosensor, bio-fluoresence imaging, drug delivery and photothermal therapy.

Simultaneously, the biocompatibility of MoS2 nanomaterials in vivo has been tapped in cancer
na

models. Currently, several in vitro and in vivo models were adopted to assess the toxic effects of

MoS2 nanomaterials on various endopoints, along with the underlying toxicological mechanisms
ur

involved in oxidative stress mediated by ROS signal pathways.

Jo

Although numerous studies have been conducted on the sythesis and applications, there are

still several new challenges and requirements in the whole life cycle assessment of MoS2

nanomaterials. Firstly, the operational performances of different MoS2 nanomaterials in

environmental and biomedical applications are highly dependent on their physicochemical

properties. Due to the different structural features (i.e., layers and crystal phase) that origined from

different synthetic methods, MoS2 nanomaterials' physicochemical properties are significantly

different. Therefore, preparing ultrathin MoS2 nanosheets and MoS2-based nanocomposites with

specific structural features and excellent performance in a highly controllable manner is a major

trend in the future.

Due to their excellent physicochemical performance, MoS2-based nanomaterials would be

broadly applied in various fields even realize industrialization in the future. Those MoS2

nanomaterials, of course, will be released into the environment, then transformed into different

media, and thus potentially affect the eco-environmental safety and human health. Most importantly,

most ultrathin MoS2 nanomaterials are lack of long-term stability and durability presently, and the

phase structure of MoS2-based nanomaterials probably transforms. The transformation process for

of
MoS2 is altered by a confluence of factors depending on the characteristics of MoS2 nanomaterials

ro
themselves and of the receiving media. In some cases, the ambient conditions may potentially

change their structural features. The transformation of phase structure of MoS2 sometimes increases
-p
their risk into the environment. Therefore, assessing the toxicity of MoS2-based nanomaterials
re
would be more important and necessary.

However, the exact implications of MoS2 toxicity are still being debated. As small differences
lP

in the physicochemical properties of MoS2 contribute to significant variation in the toxicity, it is

critical to discriminate how these variations influence toxicity. Indeed, the risk assessment results
na

can be affected by several influence factors, including MoS2' physicochemical properties,

assessment models and methods, and exposure conditions. Importantly, only a few studies using
ur

algae models have been conducted to assess their potential eco-environmental toxicity, yet more

systematic and efficacious health and environmental studies remain largely unexplored. The choice
Jo

of evaluation models, culture system, assay conditions and exposure route can also influence the

toxic responses to MoS2 nanomaterials.

Without a doubt, a fundamental understanding of the biological interactions between MoS2

nanomaterials and biological objectives (i.e., molecules, cells, tissues and organisms) is vital to the

future design of safe nanotechnologies. All in all, the influx of MoS2 is a matter of balancing
rewards and risks in the eco-environment and humans. What we can do at present is to make the

most of the advantages and avoid the disadvantages (Fig. 7). As thus, complete adequate

characterization of MoS2 nanomaterials at lower concentrations and systematical toxicity studies

along with the underlying mechanisms, of course, are essential for their optimized environmental

and biomedical applications with minimal risks for eco-environmental safety and human health.

Conflict of interest: The authors declare no potential conflicts of interest.

of
Statement of Novelty

The two-dimensional molybdenum disulfide (MoS2) nanosheets and MoS2-based nanocomposites are

ro
widely used in various fields owing to their fantastic physicochemical properties, whereas such

large-scale usage would result in potential risks on eco-environment and human health. Herein, the
-p
latest researches about their environmental and biomedical applications along with potential risks,

covering in vivo and in vitro studies, are critically summarized. Then the environmental behaviors and
re
toxicological mechanisms are illustrated. Lastly, several special phenomena about the balance between
lP

applications and risks are pointed out, thus giving guidance for harm predication and making full use

of their advantages.

Conflict of interest
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The authors declare no potential conflicts of interest.

ur

Acknowledgements
Jo

This study was supported by the National Natural Science Foundation of China (grants no.

21567014, 51878321 and 51968032), the China Postdoctoral Science Foundation (grant no.

2019M653846XB), and the Yunnan Provincial Department of Education (grant no. 2020J0060).
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 Figures (1-7)

Fig. 1 Typical crystal structures of MoS2 nanomaterials

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(A) Octahedral (1T-phase), (B) Trigonal prismatic (2H-phase) and (C) Trigonal prismatic
(3R-phase) unit cell structures. Reproduced with permission from Ref. [19, 28, 36].
Fig. 2 Typical synthetic methods of MoS2 nanosheets and MoS2-based

nanocomposites

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Bottom-up methods (i.e., hydrothermal (A1) and chemical vapor deposition (A2)) and
top-down methods (i.e., chemical exfoliation (B1), liquid-phase exfoliation (B2) and
micromechanical exfoliation (B3)) used for MoS2 nanosheets synthesis; covalent (C1) and
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non-covalent (C2) functionalization used for MoS2-based nanocomposites synthesis.

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Fig. 3 ROS-mediated environment pollutants degradation and

sterilization by MoS2 nanomaterials

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(A) The formation approaches of reactive oxygen species (ROS) by MoS2 nanomaterials under
light illumination conditions, (B) ROS promote environmental pollutants degradation, (C) MoS2
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nanomaterials used in antisepsis, (D) MoS2 nanomaterials used in ARGs removal.

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Fig. 4 MoS2 nanomaterials used in combined photothermal and

chemotherapy of cancer

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Fig. 5 An overview on the principal components of MoS2-based

nanomaterials' toxicity

MoS2-based nanomaterials

Assessment models Potential risks Influence factors

Endpoints Assessment methods MoS2' physiochemical properties
Human health risks
Cell viability
High content screening ① Particle size, morphology, and
MTT/MTS/CCK-8/WST-8 surface characteristics (e.g., layer
Skin exposure
Energy Respiratory inhalation, structure, crystal structure and
ATP content colloidal stability) affect the toxicity;
metabolism Food additive ingestion
In vitro

Nano-therapeutics ② Small differences in the

Apoptosis/necro Flow cytometry (FCM)
physicochemical properties of MoS2

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sis Fluorescent staining
that functionalized by some small
Inflammatory
ELASA
Immune responses molecules could contribute to
responses Respiratory diseases significant variation in their toxicity.
Dermal toxicity
ROS generation
Reproductive toxicity

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Antioxidant defenses Assessment models and methods
Oxidative stress Hepatic toxicity
(GSH/CAT/SOD)
LDH release …… ① The choice of different in vitro
and in vivo models can bring about
Survival rate Dead- motionless count disparate evaluation results;
(Mortality) Plate/FCM count Ecosystem stability risks
② Different evaluation methods may
Synthesis of
macromolecule
Colorimetry (chlorophyll,
protein, and nucleic acid)
-p produce different toxic results.

Exposure conditions
In vivo

Permeability of Flow cytometry ① Different culture conditions along

wall/membrane Fluorescent staining with exposure time and doses result
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in different toxic effects;
Cellular Transmission electron
ultrastructure microscope Swallow Phytotoxicity ② S e v e r a l e nvironmental factors,
Adsorption Aquatic toxicity including pH, dissolved oxygen, light
ROS generation Absorption Algal toxicity irradiation, ionic strength, and natural
Antioxidant defenses organic matters , influence the
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Oxidative stress Bioaccumulation Anti-bacterial

LDH realease Oxidative stress …… transport and transformation of MoS2
Membrane potential nanomaterials.
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Fig. 6 Schematics of the molecular events by which MoS2

nanomaterials exert their toxic effects

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(A) MoS2 nanomaterials react with oxygen or strong oxidizing agents to produce ROS under
the conditions of visible light irradiation, MoS2 nanomaterials penetrate the cell membrane or
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cytoderm in direct ways (B1) and indirect way (B2) to interact with subcellular structures, MoS2
nanomaterials exerts toxicity via oxidative stress (C1), biomacromolecules inhibition and damage
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(C2), and inflammatory response (C3).

Fig. 7 The stable balance between applications and risks of MoS2

nanomaterials

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