Nanomaterials in biomedical application

NANOMATERIALS IN BIOMEDICAL APPLICATION

By:Sumeet Sharma

M.Tech- Materials EngineeringEmail- [email protected]

Department of Metallurgical and Materials EngineeringVisvesvaraya National Institute of Technology, Nagpur, Maharashtra

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.

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

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)

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

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)

Fig. 5 Image as under flouroscent microscope


Source: Synthesis of ternary CuInS2/ZnS quantum dot bioconjugates and their applications for targeted cancer bioimagingDOI: 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.


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


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)

QD

Fig 6:mechanism of site specific flouroscent imaging


Anchor biomolecule

Target biomolecule

Bio-conjugateInoragnic 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 )


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 tocell 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


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


Immunogold labellingGold 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


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)


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 hybridEx: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)


Composite nanoparticles for treatment of cancer1. 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)

Special Thanks to- Dr. J..G. Bhatt for his guidance and suggestions

• Thanking you

Date post:	13-Apr-2017
Category:	Engineering
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