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POTENTIAL APPLICATION OF NANOPARTICLES IN

MEDICINE
Diagnosis and Therapy
Interesting fact about nanomedicine
Interesting fact about nanomedicine
Drug Delivery
A. Because of their small sizes, nanoparticles are taken by
cells where large particles would be excluded or cleared from
the body
1) A nanoparticle carries the
1 pharmaceutical agent inside its core,
while its shell is functionalized with a
‘binding’ agent

2 2) Through the ‘binding’ agent, the


‘targeted’ nanoparticle recognizes the
target cell. The functionalized
nanoparticle shell interacts with the cell
3 membrane

3) The nanoparticle is ingested inside the


cell, and interacts with the biomolecules
inside the cell
4
4) The nanoparticle particles breaks, and
the pharmaceutical agent is released
Medical Imaging
A. Optical properties of nanoparticles depend greatly on its structure.
Particularly, the color (wavelength) emitted by a quantum dot
(a semiconductor nanoparticle) depends on its diameter.

B. C. The quantum dots (QD) can be injected to


a subject, and then be detected by exciting
them to emit light

CdSe nanoparticle (QD) structure

Imaging of QD’s targeted on cellular


structures

Solutions of CdSe QD’s of different


diameter
A Quantum Dot Nanoparticle
A. The quantum dot itself (the semiconductor nanoparticle) is toxic.
Therefore some typical modifications has to be made for it to become
biocompatible. 1) The core consist of the semiconductor
material that emits lights

2) The shell consist of an insulator material


3 that protects the light emitting properties
of the QD in the upcoming
2 functionalization

3) The shell is functionalized with a


biocompatible material such as PEG or
1 a lipid layer

4) Additional functionalization can be done


with several purposes (e.g. embed a
4 drug for drug delivery, or assemble an
antibody to become the QD target-
specific
Diagnosis and Sensing
A. Diseases can be diagnosed through the (simultaneous) detection of a (set of)
biomolecule(s) characteristic to a specific disease type and stage (biomarkers).

Nanoparticle
B. Each cell type has unique D. Coating molecule
molecular signatures that specifically attracted
to the molecular
differentiate healthy and sick signature
tissues. Similarly, an infection
can be diagnosed by detecting
molecular signature of
the distinctive molecular
sick cell of infecting
signature of the infecting agent
agent (e.g. an antibody)
C. A nanoparticle can be
functionalized in such a way
that specifically targets a Cell membrane
biomarker. Thus, the
detection of the nanoparticle is
linked to the detection of the
biomarker, and to the
diagnosis of a disease
Nanoparticles in action
A. Modifying a ferromagnetic nanoparticle with human immunoglobulin G
(IgC), which specifically binds the protein A in the cellular wall of
staphylococcus, the bacteria can be detected through a MRI test

B. C.

Accumulation of functionalized
ferromagnetic nanoparticles on
staphylococcus

Negligible accumulation of nanoparticles in Directed accumulation of dangerous bacteria by


absence of functionalization conjugation with functionalized magnetic
nanoparticles
THERAPY
Gold Nanoparticles vs. Alzheimer
A. Alzheimer and other B.
degenerative diseases are
caused my the clustering of
amyloidal beta (Aβ) protein.

Alzheimer’s brain Healthy brain


C.
D.
Gold
nanoparticles can
be functionalized to
specifically attach
to aggregates of
this protein
(amyloidosis)
Functionalized nanoparticle Chemical structure of Aβ-
protein
Gold Nanoparticles vs.
Alzheimer
A. The functionalized gold nanoparticles selectively attach to
the aggregate of amyloidal protein. The microwaves of
certain frequency are irradiated on the sample. Resonance
with the gold nanoparticles increases the local temperature
and destroy the aggregate

Before irradiation After irradiation


FABRICATION
The nanofabrication processes can be divided into
two well defined approaches:
1) ‘top-down’ and
2) ‘bottom-up’
Definition generally dictates that in the ‘top-down’ approach
it all begins from a bulk piece of material, which is then
gradually or step-by-step removed to form objects in the
nanometer-size regime

Well known techniques such as


photo lithography
electron beam lithography
anodization
ion- and plasma-etching, all belong to this type of
approach
The ‘bottom-up’ approach on the other hand takes the idea that
it all begins from atoms and molecules that get
rearranged and assembled to larger nanostructures

It requires a thorough understanding of the short range forces of


attraction such as
Van der Waals forces
electrostatic forces
and a variety of inter-atomic or intermolecular forces
TOP-DOWN APPROACH
BOTTOM- UP APPROACH
BIOLOGICAL APPROACH
PDMS Mold

Highly doped Si wafer Highly doped Si wafer Highly doped Si wafer

PDMS Mold

Highly doped Si wafer Highly doped Si wafer Highly doped Si wafer

PDMS: Polydimethyl Siloxane


Typically the sol is first formed by mechanically mixing a liquid alkoxide
precursor, such as
tetramethoxysilane (TMOS) or tetraethoxysilane (TEOS) with water
and a cosolvent together with an acid or base catalyst at room
temperature

During this step, alkoxide groups are removed by acid- or base-catalyzed


hydrolysis reactions and networks of O-Si-O linkages are formed in
subsequent condensation reactions

Depending upon the water:alkoxide molar ratio R, pH, temperature, and


solvent,
further condensation leads to different polymeric structures such as
linear
entangled chains
clusters and colloidal particles
The resulting sol is then cast into a mold, whereupon it is
heated up to get rid of the solvent and this gelation causes the
formation of a solid in the shape of the mold

The gel is aged to allow its network to strengthen and it is then


dried under atmospheric conditions to remove the liquid

Sol-gels prepared in this way are called Xerogels

These structures have


large surface-to-volume ratios
high pore connectivity
and narrow pore size distributions and can be
doped with a variety of organic/inorganic materials during the
mixing stage of the sol-gel process
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