Beruflich Dokumente
Kultur Dokumente
GEK 1540
Frank Watt Dept of Physics
1. Fibre optics and endoscopy: Reaching the parts not easily reached.
Contents:
Nanotechnology and Nanomedicine: What is it?
Nanomedicine and drug delivery.
Nanomedicine using magnetic nanoparticles
Nanotechnology and nano-robots.
Nanoparticle toxicology?
Note: The contents of this chapter describe a possible future for nano-
technology in medicine. Most of this work is at the research stage or
futuristic and should not be taken as definitive knowledge!
Nanotechnology and Nanomedicine: What is it?
Fullerenes: Buckyballs and Carbon tubes: Carbon based, lattice-like, potentially porous
molecules. Buckyballs are spherical in shape while carbon tubes are cylindrical.
Dendrimers: Dendrimers are highly branched structures gaining wide use in nanomedicine
because of the multiple molecular "hooks" on their surfaces that can be used to attach
cell-identification tags, fluorescent dyes, enzymes and other molecules.
Quantum dots: Nano-sized semiconductors that, depending on their size, can emit light in all
colours of the rainbow. They act like giant atoms (with electron transitions emitting
visible photons) quantum confinement.
Nanorods: Typically 1-100 nm in length, nanorods are most often made from semiconducting
materials and used in nanomedicine as imaging and contrast agents.
http://biotech.about.com/od/nanotechnology/a/typesnanopart.htm
Examples of nanoparticles.
Transmission electron
microscope images Bottles of liquid containing different
(TEM) of 15nm Fe3O4 sized CdSe quantum dots (1 5nm).
magnetic nano- The dots fluoresce with a colour Examples of carbon nanotubes
particles depending on their size.
http://en.wikipedia.org/wiki/
Nanomedicine and drug delivery
(a) NPshavereduceddimensionsandthe
abilitytopenetratecellmembranes
withoutmodifyingtheirintegrity.
(b) Thepossibilitytoundergosurface
functionalization (chemicalmodification)
soastomakethenanoparticles soluble
inwater(ie toavoidaggregation)eg
usingPEG(PolyethyleneGlycol).
(c) Thepossibilitytoundergosurface
functionalization soastotargetthe
nanoparticles andthereforedrugs,to
specificcellsandcellorganelles.Eg folic
acidforcancercells.
(d) Thepossibilitytoundergosurface
functionalization soastodeliverdrugsto
thetarget(eg theanticancerdrug
Paclitaxel).
Nanoparticle targeting and drug delivery
Chemical functionalization of Au NPs, QDs and CNTs with drug molecules and targeting agents.
Example:Cancertreatment:
Thecellsurfacereceptorforfolicacid(folate receptor)doesnotfunctionin
healthycellsbutisexpressedonthesurfaceofcancercells.
Functionalised theNPswithPEGsurfacemodification(inordertomakethem
solubleinwater,andnotaggregate).
Functionalise theNPswithfolicacid(soastoonlytargetcancercells)
Inthiswaythecancerdrugistargetedonlytocancercells.TheNPspenetrate
thecancercellwall,andthePaclitaxel killsthecell.Inprinciplethisspecific
targetingwillreducesideeffectsofthedrug..
The disease usually remains undetectable until a heart attack or stroke happens.
It would be good to have some means of identifying any disease progression.can
we identify increased inflammation or macrophage activity?
Nanomedicine using magnetic nanoparticles
b) Image enhancement using magnetic nanoparticles
Brief description:
Methods and Results: To test the hypothesis that nanoparticle-enhanced, high-resolution MRI can
measure plaque macrophage accumulation in vivo, we employed a 3.0 Tesla magnet with clinically-
approved, phagocyte-targeted super-paramagnetic iron oxide (MION47, 10 mgFe/kg, iv) in 6 cholesterol-fed
New Zealand White rabbits 6 months after balloon injury.
MRI visualized in vivo thickened abdominal aortas on T1 and T2-weighted spin echo (T1SE, 20 axial
slices/animal; T2SE, 28 slices). Images 72 hours after MION47 injection exhibited signal reduction
(darkening) in aortas on T2SE (signal intensity ratio: aortic wall/muscle; pre 1.44 0.26 vs. post 0.950.22,
165 slices, p<0.01) while T1SE showed no significant effect. MRI also demonstrated ex vivo darkening of
aortas on T2 weighted images in MION47-injected rabbits unlike control aortas (no injection).
Histological assays further colocalized iron accumulation (Prussian blue staining) with immunoreactive
macrophages in the intima, and correlated the magnitudes of T2 darkening in vivo with macrophage areas in
situ (155 slices, r =0.77, P<0.01). Moreover, in vitro validation studies revealed a concentration-dependent
MION47 uptake and shortened T2 relaxation time during differentiation of human primary macrophages.
Conclusion: MION47-enhanced MRI can detect plaque macrophages in vivo, offering the important
information on inflammatory burden in atherosclerosis
Nanomedicine using magnetic nanoparticles
c) Destruction of cancer cells using magnetic nanoparticles
http://www.foresight.org/Nanomedicine/Gallery/Captions/
Nanotechnology and nano-robots.
In an artist's conception, a
microscopic robot cleans
deposits from a blood
vessel in order to prevent
atherosclerosis.
Researchers predict the
creation of microscopic
robotic devices that will
patrol the human body and
fight disease.
Tom Herzberg
Video: Nanobots
cleaning an artery wall.
http://www.foresight.org/Nanomedicine/Gallery/Captions/
Nanoparticle toxicology
Free radical damage: Iron nanoparticles range in size from a diameter of ~20
nanometers to superparamagnetic particles of iron oxide (SPIO) with a diameter
of ~100 nanometers. These iron particles can catalyse free radicals (eg OH-)
which can cause DNA damage and cell death.
To counteract this toxic effect, the iron nanoparticle can be coated in
dextran (a polysaccharide made of many glucose molecules), which
protects the cell against free radical damage..
Conclusions:
The use of nanoparticles and nanotechnology in
biomedicine shows great potential, but much more
work (research and development) needs to be carried
out on the applications (to see if NPs offer
advantages over existing techniques), and on any
potential toxicology.