NANOTECHNOLOGY-AND-NANOMEDICINE.

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BdeBiomedica

Introducción a la Bioingeniería

1º Grado en Ingeniería Biomédica

Escuela Politécnica Superior. Campus de Leganés

Universidad Carlos III de Madrid

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 NANOTECHNOLOGY
AND
NANOMEDICINE

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 NANOTECHNOLOGY AND NANOMEDICINE
- Definitions
- Why is nanotechnology different?

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- Nanoparticles
- characterization techniques

1 DEFINITIONS
Nanotechnology: creation and utilization of materials, devices, and systems through the control of matter
at the nanometer-length scale., at the level of atoms, molecules, and supramolecular structures.

Nanomedicine: medical application of nanotechnology, coined to define the use of nanoscale structures
that are used to deliver drugs or diagnosis within the human body.

Nanoparticles: chemical compound in the mesoscopic scale, with at least one dimension smaller that 100-
150nm. There should be new or improved properties compared with bulk material due to their nano size.

Mesoscopic scale; that one between the macroscopic and atomic scales. (It has to be really small to not
collapse veins…)

Aggregation: natural tendency to form big lumps and precipitate due to weak interactions between particles
(van der Waals, electrostatic…).

2 WHY IS NANOTECHNOLOGY DIFFERENT?

1- Quantum effects dominate the behavior of matter. > hanoparticles : new properties
2- Much of the biology occurs at this scale.
3- Surfaces and interfaces play a fundamental role in the physicochemical properties.

2.1 QUANTUM EFFECTS DOMINATE THE BEHAVIOR OF MATTER

• When particles sizes of solid matter in the visible scale are compared to what can be seen in a
regular optical microscope, there is little difference in the properties of the particles.
• Properties of materials are size dependent in this scale range.
• When particles size is made to be nanoscale, physical properties change as function of the size of the
particle.

2.2 MUCH OF THE BIOLOGY OCCURS AT THIS SCALE

• Many of the inner working of cells naturally occur at the nanoscale.
• For example hemoglobine is 5.5 nm in diameter or a strand of DNA is only about 2nm in diameter

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 2.3 SURFACES AND INTERFACES ARE FUNDAMENTAL FOR PHYSICOCHEMICAL
PROPERTIES
• Higher reactivity
• Better catalysts
• Multifunctionalities

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3 NANOPARTICLES
STRUCTURE OF NANOPARTICLES COMPONENTS: core and surfactant
D

Composition of the core: Au, Ag, Fe2O3, SURFACTANT: it is on the surface

&
Gd2O3, MnFe2O3, SiO2, ZnO, CdSe,
Polymers… → Technique

Type of surfactant Organic Molecules,

hydrophobic polymers, proteins,
antibodies… → Biology

Size: function of the final application, 5nm

– 200nm

MAIN APPLICATIONS: Imaging/Therapy/

Theragnosis

BIOMEDICAL APPLICATION: BIOCONJUGATION

Bioconjugation: chemical strategy that couples a chemical compound and a biomolecule together.
se

Chemicacompon
a
All knowledge that it is involved.

4 CHARACTERIZATION TECHNIQUES
(we use different techniques no get different information)

4.1 TRANSMISSION ELECTRON MICROSCOPY TEM)

To get high quality pictures with high resolution by applying an electro beam (haz) through an ultra-thin sample,
interacting with the sample as it passes through.

Metallic nanoparticles are used.

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 WHAT DO WE GET? → the state of aggregation, core size, shape. In the image we see the core, we visualize the
changes in density in metallic nanoparticles.

electro
beam >
-
high quality
-
image

ultra
thin

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sample
METALLIC
NANOPARTICLES

4.2 DYNAMIC LIGHT SCATTERING core + surfactant

It measures the size of the whole nanoparticle ( HD size) in a liquid by analyzing the fluctuations in the
light (medium) intensity at different time increments.

The reported hydrodynamic size is a function of the core size (TEM), the surfactant and the ionic
strength >>> real NPS

Pdl : polydisperse index DLS (ideally the PDL has to be <0.2) To know the dispersion of the particles

TO BE A GOOD
·

·
only
narrow
one
e Explicar
gráicos!!!!

SAMPLE :

mountain

-
two
different populations
MAIN APPLICATIONS we cannot this in the
Only
narrow
one
population
>
-
GOOD
and

OPTION
inject
body (we don't know the
efects
Imaging: AuNPs, IONPs, QD

Therapy: Liposomes, micelles, exosomes

5 EXAMPLES
· non toxic

E very magnetic
·

5.1 IRON OXIDE NANOPARTICLES (MR IMAGING) ·

contrast
agent in MRI

Ternary iron oxides with cubic Inverse Spinel structure

It is nontoxic and it is used in many clinical studies and FDA approved for some applications.
Large saturation magnetization (90 emu/g).
It is the most widely investigated type of magnetic nanoparticle for biomedical application.
Iron and oxygen → property: superparamagnetic

(Not toxic, very magnetic. They are more magnetic because of the magnetic domain. They are useful for
MRI as a contrast agent because they are superparamagnetic)

HOW DOES IT WORK? A domain is a group of spins whose magnetic moments are in the same direction,
and in the magnetization procedure, they act cooperatively.

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 ifferent directions
MAGNETIC DOMAIN D - Differenten
only direction
same
- superparamagnetic

*
line
the

Hysteresis loop (to know if they are paramagnetic): as the external field with the signal from the
microphone is turned off, the little magnetic domains in the tape don't return to their original
configuration.

Any magnetic stuff even without a magnetic field, they have magnetic properties. A superparamagnetic
# component doesn’t have magnetic properties if there is not a magnetic field but as soon as there is, they
① are VERY magnetic.

When the magnetic field applied to a ferrofluid is removed, the magnetization of the ferrofluid relaxes
back to zero due to the ambient thermal energy of its environment.

Two mechanisms are responsible for this relaxation:

• Brownian rotation which is the physical rotation of the particles themselves within the fluid
• Neel relaxation, which is the rotation of the atomic magnetic moments within the particle.

MAIN APPLICATIONS
Therapy: Drug delivery (Radiotherapy combined with MRI) / Hyperthermia- Thermal ablation
(Musculoskeletal system associated diseases)

Diagnosis: In vivo (MRI) / In vitro (Sensing, cell sorting, bioseparation, enzyme immobilization,
immunoassays, Transfection Purification)

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 SYNTHESIS
Decomposition of an organometallic precursor in an organic media in presence of a surfactant

High temperature decomposition of organic precursors:

• ADVANTAGES:

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Narrow particle size distribution
No aggregation
Oxidation control
Large scale synthesis
• DISADVANTAGES:
Unstable in aqueous media

5.2 GOLD NANOPARTICLES (BIOSENSORS AND CT CONTRAST AGENT)

MAIN PROPERTIES
▪ optical properties (colors)
▪ size-dependent electrochemistry
▪ high chemical stability

Gold nanoparticles display

shape and size- dependent
properties. Often red, but many
other colors are possible.

· IMPORTANT CONCEPTS
▪ Surface plasmon resonance (SPR) is the collective oscillation of electrons in a solid or liquid
stimulated by incident light.
▪ The resonance condition is established when the frequency of light photons matches the natural
frequency of surface electrons oscillating against the restoring force of positive nucleo.
▪ SPR in nanometer-sized structures is called localized surface plasmon resonance.

There is color absorption and a electric field is created.

APPLICATIONS X-ray drug delivery sensors

X-RAY IMAGING

AuNPs serve as a contrast agent for CT imaging.

It has a better X-ray absorption coefficient compared to the traditional iodine. Also,it is easier to
manipulate, nontoxic, surface is more stable and it is better for targeted delivery. (better AuNPs than
iodine)

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 a
E
-
-
Common vascular contrast agents such as iodinated molecules have a problem because the blood
circulation time is short and is rapidly eliminated through the kidneys. Hence, a short imaging window
e may require multiple injections with the risk of developing thyroid dysfunction.

DRUG DELIVERY

It has a high surface area for loading the density of drugs, stability and nontoxicity make them an

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efficient nanocarrier in drug delivery systems (DDSs).

These effective nanocarriers can transfer various drugs such as peptides, protein, plasmid DNAs
(pDNAs), small interfering RNAs (siRNAs), and chemotherapeutic agents.

Besides the spherical nanoparticles, recent researchers have proposed stable colloidal gold nanorods as
an appropriate agent for drug delivery.

PEGylated Au NRs have provided a sufficient drug transfer by avoiding the reticular-endothelial system
(RES) clearance.

SENSING

One of the major applications of AuNPs is in chemical and biological sensing.

Using intrinsic features, Au NPs have been used as efficient sensors for the
detection of different analytes such as metal ions, anions, and molecules like,
saccharides, nucleotides, proteins and toxins.

AuNPs sensors can be colorimetric, fluorescence-based, electrical and

electrochemical, surface plasmon resonance, surface enhanced Raman scattering (SERS)-based…
Different types of nano-biosensors have employed special features of AuNPs.

5.3 LIPOSOMES (DRUG DELIVERY SYSTEMS)

Liposome→ Microscopic sphere made from fatty materials, predominantly phospholipids.

It protects the compound, and we avoid its presence in other organs.

It a natural compound that it’s already in our cell membrane. The liposome fusions with the membrane
so it can deliver drugs inside (that maybe are hydrophobic) or outside the hydrophilic.

They are easy to synthesize.

They are less stable, maybe allergic (toxic effect), high cost , … but overall it’s very good and it has many
applications.

ADVANTAGES

➢ Suitable for delivery of hydrophobic, hydrophilic, and amphipathic drugs & agents

➢ Chemical and physically well characterized entities.

➢ Biocompatible

➢ Suitable for controlled release

➢ Suitable to give localized action in particular tissues

➢ Suitable to administer via various routes

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 DISADVANTAGES

➢ Less stability

➢ Batch to batch variation

➢ Difficult in large scale manufacturing and sterilization

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➢ High production cost

➢ Sometimes phospholipids undergoes hydrolysis and oxidation reactions

➢ Leakage and fusion

➢ Allergic reaction may occur with liposomal constituents

➢ Synthetic origin → toxicology

EXOSOMES AS DDS
Nowadays , we use exosomes as natural liposomes because liposomes are very biocompatible but they
are synthetic, so exosomes are better

EXOSOMES AND IMAGING

=>
It goes directly to where you want it to go, the drug is inside the nanoparticle.

It is good because maybe your body don’t accept the drug if you inject it directly.

The treatment is much more specific. ↑

5.4 THERAGNOSIS (THERAPY + DIAGNOSIS)
It is the same molecule for therapy and diagnosis.

For example, iron nano particles (diagnosis MRI and hyperthermia) or isotopes
--
(contrast agent) (burn tissue)

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 KEYPOINTS:
• Nanoparticles, properties? : important size (nano) to not collapse the veins, it’s important that
they have new properties (iron- superparamagnetic/ Au – optical properties)
• Structure:
o Core (important because of physical properties)
o Surfactant (biological application)
• Characterization: DLS and TEM (TEM is not useful for liposomes because they are not dense
enough)
• IONPs
o Property: superparamagnetic
o Application: we use it for diagnosis and as a contrast agent in MRI and therapeutic to
repair tissue
• Liposomes: we can put the drug inside ( if it is hydrophobic we put the drug in the membrane
(layer) if it is hydrophilic (se disuelve en agua) put it in the core
• Theragnosis: Isotopes (as iodine) for PET/SPECT

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