This document discusses nanomaterials and their biomedical applications. It begins by defining nanomaterials as objects with at least one dimension between 1-100 nanometers. It then classifies nanomaterials and discusses some common terms like nanoshells and quantum dots. The document focuses on the biomedical applications of nanomaterials, including biological imaging using quantum dots, targeted drug delivery using nanoparticles, and cancer treatment using magnetic nanoparticles. In summary, the document outlines different types of nanomaterials, their properties, and various ways they can be used for biomedical purposes such as imaging and targeted drug delivery.
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Nanomaterials in biomedical application
1. NANOMATERIALS IN
BIOMEDICAL APPLICATION
By:
Sumeet Sharma
M.Tech- Materials Engineering
Email- sumeetsharma005@gmail.com
Department of Metallurgical and Materials Engineering
Visvesvaraya National Institute of Technology, Nagpur, Maharashtra
2. WHAT ARE NANOMATERIALS AND
NANOPARTICLES??
• one external dimension in the size range from approximately
1-100 nanometers
• Nanoparticles are objects with all three external dimensions
at the nanoscale
CLASSIFICATI0N OF NANOMATERIALS:
Fig1:Schematic classification of nanomaterials (a)3D (b)2D (c)1D (d)0D
(a) (b) (c) (d)
Source:V.Pokropivny,R.Lohmus,I.Hassainova,A.Pokropinvy;Introduction in nanomaterials and nanotech.;Univ. of TARTU,2007,225p.
3. Some common terms in nanomaterials
• Nanoshells are nanoparticles that consist of an
inner core of one type of material and an outer
layer of another only a few nanometers thick.(fig
2(a))
NANOSHELLS
QUANTUM DOTS
• Quantum dots are tiny particles, or
“nanoparticles”, of a semiconductor material,
traditionally chalcogenides (selenides or
sulfides) of metals like cadmium or zinc (for
example CdSe or ZnS), which range from 2 to 10
nanometers in diameter(fig 2(b))
Fig 2(a) model of gold Nanoshell
Fig 2(b) Quantum dots
4. Imaging method…
Confocal microscopy
• light is incident on a molecule, it may absorb the light and then emit light
of a different color, a process known as fluorescence.
Fig 3 showing confocal microscopy(a) shows
mechanism of flourescence (b) shows rejection
of light not incident on focal plane (c) shows
basic setup of confocal microscopy
Source:confocal microscopy,Denis Semwogerere;Eric R.Weeks,Emory Univ.,Atlanta,Georgia,USA
(a)
(b)
(c)
5. Biomedical applications of nanomaterials
• Biological imaging using quantum dots
• Immuno flouroscent biomarker imaging
• Target specific flouroscent imaging
• Immunogold labelling
• Targeted drug delivery using nanoparticles
• Gold nanoshells for immunoassay and cancer
detection and therapy
• A carbon nanotube field emission multipixel x-
ray array source for microradiotherapy
application
6. Biomedical applications of nanomaterials …
Biological imaging using quantum dots
• In vivo targeting ZnS capped CdSe quantum dots
coated with lung targeting peptide via Thiol exchange
reaction accumulate in the lungs of mice.
• These ZnS capped CdSe QDs emit under green and
red light 550nm and 625nm flouroscence
maxima,respectively.
Source: Ackerman M.E.,W.C.W. Chan,P.leakkemen,PKAS,99(2002
Fig. 4 In vivo target imaging using
ZnS capped CdSe QDs
(a) With lung targeting peptides
(b) With peptides and PEG
(a) (b)
7. Fig. 5 Image as under flouroscent
microscope
Biomedical applications of nanomaterials …
Source: Synthesis of ternary CuInS2/ZnS quantum dot bioconjugates and their applications for targeted cancer bioimaging
DOI: 10.1039/B916663G
• These QDs were injected into tail vein of mice ,it was then it was frozen
sectioned and examined under an inverted flouroscent microscope or
confocal microscope
• Adding polyethylene glycol [PEG] to quantum dots prevents non selective
accumulation of QDs in reticuloendothelial tissues.
8. Biomedical applications of nanomaterials …
Immuno flouroscent biomarker imaging
• QD can be used as core shell with antibodies
anchored to it,for ex.CdSe-ZnS capped with
polyethylene glycol(PEG) this is termed as QD-
PEG
• PSMA is known biomarker for diagnostic and
therapeutic applications in prostate cancer
9. Biomedical applications of nanomaterials …
Target specific flouroscent imaging
• Antibody of prostrate selective membrane antigen (PSMA-Ab)
is anchored.Target molecule is antigen present in cell
membrane
• PSMA is only present in cell membrane of a prostrate cancer
cell(C4-2)
Fig 6:mechanism of site specific flouroscent
imaging
10. Biomedical applications of nanomaterials …
Anchor biomolecule
Target biomolecule
Bio-conjugate
Inoragnic nanoparticle
Fig 7: Hybridization of conjugate biomolecules on inorganic nanoparticle surface
Source: Nisman R.,G. Dellaire,Y.Ren,R.Li,Cytochem.,52(2004),p.p. 13-18
Mechanism-Hybridization of antibody on the nanoparticle surface with the
antigen present on the cell wall of cancer cell - bioconjugate formation (fig 3 )
11. Biomedical applications of nanomaterials …
3 cases
Flouroscent
staining happens
(fig5: (a))
Reason:presence of
antigen containing
cancer cell and
antibody capped
nanoparticles(QD-
PSMA)
QDs doesnot attach
to cell wall surface
(fig5: (b))
Reason: QDs are
not anchored
with antibody
QDs doesnot attach to
cell wall surface even
though they are
anchored with
antibody(fig 5: (c))
Reason: absence of
target antigen cell wall
or non-cancerous PC-
3 cells
Target specificity
12. Biomedical applications of nanomaterials …
Fig 8:Prostate specific
membrane antigen (PSMA)
targeted nanoparticles for
imaging and therapy of
prostate cancer
Source: Sachin S. Channdran,Sangeeta Ray,Martin
G.Pomper, Pub.no.US20110200677 A1
Fig 9: Various interactions of QDs
Flouroscence
image
Brightfield
image QD-
PSMA with
C4-2 cancer
cell
Brightfield
image
Brightfield
image
QD-PEG with C4-2 cells QD-PSMA with PC-3 Cells
Flouroscence
image
(negative
staining)
Flouroscence
image
(negative
staining)
(a) QD-PSMA with C4-2 cancer cell (b) (c)
Source: Nisman R.,G. Dellaire,Y.Ren,R.Li,Cytochem.,52(2004),p.p. 13-18
13. Biomedical applications of nanomaterials …
Immunogold labelling
Gold particles Immuno targetted Immunogold
Gold particles are used as
labels for imaging cell lines
and tissues
• Immunoglobulin 1g G-capped Gold nanoparticles used for imaging pathogenic
organisms like staphyloccocus aureus,staphyloccocus pyrogenes,staphyloccocus
saprophyticus.
•1g G can bind specifically to pathogens produced by Bacteria , thus it is used to
image Bacteria by TEM
•No labelling when citrate capped and BSA-capped gold nanoparticles are used
Fig 10: TEM image of Staphyloccocus Saprophyticus by
incubating these bacteria with Au-1g G-nanoparticle
Source: C.W. Chan,S.Nie,Science,281(1999),pp. 2016-18
14. Biomedical applications of nanomaterials …
Fig 11: (a)(b)(c)(d) high reflectance confocal images of SiHa cells labelled with
anti EGFR/Au conjugates.(e)(f)Nonspecific labelling using Au conjugates with BSA
Laser scanning confocal
reflectance
Combined confocal
reflectance/transmittance
(a)
(c)
(e)
(b)
(d)
(f)
15. Biomedical applications of nanomaterials …
Targeted drug delivery using nanoparticles
• Slow and selective release of drugs to the targeted organs
• 2 kinds of nanomaterials used:
(1)organic
(2)organo-inorganic hybrid
Ex:Antibacterial activity of Vancomycin capped Au nanoparticles
Imp:
minimum inhibitory concentration was lower (1/50 of pure vancomycin)
Efficiently binds with bacteria
Also acts against vancomycin resistant E.Coli bacteria
Fig 12:TEM image of E.Coli being treated by Au@van
Au@van
Source:Gu H.,P.L.Ho,E.Tong,L.Wang,B. Xu;Nano. Letter,3(2003,pp.1261-3)
16. Biomedical applications of nanomaterials …
Composite nanoparticles for treatment of cancer
1. Use of magnetic nnoparticles carrying active drugs,for ex:anticancer drug
mitoxantrone adsorbed to magnetic iron oxide nanoparticles which were
held together and stabilized by dextran matrix,addition of responsive
component like Au nanoparticles can further help to trigger release of
anticancer drug locally by photoinduced heating.
(Sources: (1)Alextou C.,Arnold W.,Klein R.J.;A.S. Locoregional cancer treatment with magnetic drug trgetting,cancer res.2000,60,6641-6648
(2)Skirtach A.G.,Munoz-Javler A.,Kreft O.,Kohler K.,Laser induced release of encapsulated materials inside liing cells,Angew. Chem.,int. ed. 2006,45,4612-4617)
2. Local heat generation by optical excitation of gold nanoparticles can
destroy tumor cells,this therapy is called hyperthermia
(Jain R.K.,Transport of molecules,particles and cells in solid tumors,ann.rev. Blomed.eng.,1999,1,241-263)
3. Microwave irradiation of magnetic and gold nanoparticles,destrot tumor
cells by heat
(Pankhurst Q.A.,Conolly J.,Jones S.K.,Applications of magnetic nanoparticles in Biomedicine.J.Phys.D:Appl.Phys.,2003,36,R167-R181)
4. Photodyanamic therapy making use of photosensitizing
molecules(porphyrins) as active components,which are activated by
light(near IR region),releasing reactive Oxygen species(ROS),which cause
tumor regression
(Bakloa R.,Ohba H.,Zhelev Z.,Ishikawa M.;Quantum dots as Photosnsitizers,Nat.Biotechnol.,2004,22,1360-1361)
17. Special Thanks to- Dr. J..G. Bhatt for his guidance and suggestions
• Thanking you