Nanomaterials for Biological Applications

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Nanomaterials for Biological Applications
M. Eswaramoorthy JNCASR eswar_at_jncasr.ac.in www.jnc
asr.ac.in/eswar
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A Nanomaterial has at least one of its dimensions
in the nanometric regime
Clusters, Nanoparticles
A block of metal
Missing dimension falls in the Quantum Regime!
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• Usually exhibit characteristic physical and
  chemical properties different from the bulk as a
  consequence of having at least one spatial
  dimension in the size range of 1-1000 nm.

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Examples of Nanomaterials
Size (dia.)
Materials
Nanocrystal and clusters Other
nanoparticles Nanowires Nanotubes Nanoporous
solids 2-D array of nanoparticles 3-D
structures(superlattices) Surfaces and thin films
1-10 nm 1-100 nm 1-100 nm 1-100 nm 0.5-10
nm nm2 - µm2 Several nm in 3-D thickness 1-1000
nm
Metals, semiconductors, magnetic
materials Ceramic oxides Metals,
semiconductors, oxides, sulfides Carbon, layered
metal chalcogenides Zeolites, phosphates Metals,
semiconductors, magnetic materials Metals,
semiconductors, magnetic materials A variety of
materials
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• At the Nanoscale..
• Properties of metals and semi-conductors
  (electronic, optical, thermodynamic, magnetic)
  are in between bulk and atoms/molecules.
• Size dependent
• Surface area is very high
• Surface atoms to bulk ratio is more

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At the Nanoscale

• Metal can become non-metal!
• Hg at 1-2 nm level shows non-metallic band-gap
  (300 atoms are needed to close the gap)
• Even the inert gold become very active
• catalyst at 2 nm size. The color also changes
  from gold to red, purple etc.,
• Melting temp. of 2 nm CdS is around 800 ºC and
  for bulk CdS is around 1700 ºC

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Colour is associated with collective
oscillation of electrons in the conduction
band. -Surface Plasmon Resonance absorption
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Quantum Dots
CdSe Quantum Dots in hexane

• Origin of color due to quantum confinement of
  electrons
• Smaller the quantum dot, larger the band gap,
  higher the exciton absorption and emission
  frequency.
• Colour tuned with particle size!

http//web.mit.edu/chemistry/nanocluster/home.html
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Abalone shells
Mollusc shell
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Inner region- aragonite
Outer layer -calcite
Prismatic layer Nacreous layer
50µm
1µm
Mollusc shell made up of both calcite and
aragonite- spatially separated in distinct part
of the shell!
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• In nacreous layer, the aragonite polygonal
  tablets(500 nm thick) sandwiched between thin
  sheets(30 nm thickness) of protein-polysaccharide
  matrix.
• It reduces the number of voids in the shell wall
  and so inhibits propagation of cracks by
  dissipating the energy along the organic layers
  rather than through the inorganic crystals.
• Nacre 3000 times as tough as inorganic aragonite!!

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A Sheet-like B Globular C fibrillar
TEM image of silica nanoparticles present in some
cell wall of the leaves
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A tongue to scar! 7 cm long.
Goethite crystals, a-FeOOH (50 nm)
600 nm
Limpets and chitons (sea urchin) have unusual
dining habits. Scraping the algae off the
intertidal rocks using this radula.
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Crystal morphologies and intracellular
organization of magnetite nanoparticles inside
magnetotactic bacteria a) cubooctahedral b)
bullet-shaped c-d) pseudohexaganol Bars are 100
nm. E. Bauerlein, Angew Chemie Int Ed, 2003
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Ferrihydrite (5Fe2O3.9H2O) 5 nm
20 nm
Cross-section of ferritin molecule with
polypeptide shell and mineral core
Discrete nanoparticles of ferritin
Acts as a buffer in regulating the levels of free
iron Protects the cells from the pathology of
iron overload.
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Liposomes
Liposomes are soft drug delivery systems loaded
with drug in their interiors. Liposomes have
the ability to fuse with the cell membrane to
deliver the drug in to the cell
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Porous nanoparticles (MCM 41)
For drug delivery
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F. Caruso et al, Adv. Mat. 2010
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Drug Delivery Systems
Mesoporous silica Nanoparticles
Photo induced Release
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Fe3O4 _at_ Silica
For MRI and Photothermal
Fe3O4 _at_ Au
J. Shi et al, Adv. Funct. Mat. 2008
N. J. Halas et al., Nano Lett. 2006
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Photothermal cancer treatment by Au nanocages
Au cages shows strong SPR absorption in NIR
region where the absorption by blood and tissue
is minimal. Large absorption cross-section
facilitates the Conversion of NIR absorption
into heat
SKBR-3 breast cancer cells treated with
immuno (anti-HER2)-Au nanocages and then
irradiated by 810 nm laser for 5 min. Shows a
well-defined circular zone of dead cell c)
Calcein AM assay and d)Ethidium
homodimer-1(EthD-1). e, f) Without immuno-Au
cages Green colour Living cells Red colour-
Dead cells
Xia et al, JACS 2006 Warsen et al, Nano Lett,
2007
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Semiconductor nanoparticles
Metal nanoparticles
For imaging and colorimetric sensors,
photothermal treatment
Susie Eustis and Mostafa A. El-Sayed, Chem Soc.
Rev, 35, 209, 2006
http//web.mit.edu/chemistry/nanocluster/home.html
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C. A. Mirkin, Nature 1996, 382, 607
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IMAGING
Optical Imaging
MRI- Magnetic Resonance imaging Magnetic
nanoparticles are used as MRI contrast reagents.
BRET- bioluminescent resonance energy transfer
Brain showing tumor

Nature Biotechnology 24, 339 - 343 (2006)
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Companies involved in nanoparticle
commercialization
Company Major area of activity Technology
QuantumDot Corporation Luminescent biomarkers Bioconjugated semiconductor quantum dots
Smith Nephew Acticoat bandages Nanocrystal silver is highly toxic to pathogenes
PSiVida Ltd Tissue engineering, implants, drugs and gene delivery, bio-filtration Exploiting material properties of nanostructured porous silicone
Nanoshpere, Inc Gold biomarkers DNA barcode attached to each nanoprobe for identification purposes, PCR is used to amplify the signal also catalytic silver deposition to amplify the signal using surface plasmon resonance
Salata, J Nanobiotechnology. 2004 2 3
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Company Major area of activity Technology
Advectus Life Sciences Inc. Drug delivery Polymeric nanoparticles engineered to carry anti-tumour drug across the blood-brain barrier
Alnis Biosciences, Inc. Bio-pharmaceutical Biodegradable polymeric nanoparticles for drug delivery
Argonide Membrane filtration Nanoporous ceramic materials for endotoxin filtration, orthopaedic and dental implants, DNA and protein separation
BASF Toothpaste Hydroxyapatite nanoparticles seems to improve dental surface
Capsulution NanoScience AG Pharmaceutical coatings to improve solubility of drugs Layer-by-layer poly-electrolyte coatings, 850 nm
Salata, J Nanobiotechnology. 2004 2 3
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Company Major area of activity Technology
Eiffel Technologies Drug delivery Reducing size of the drug particles to 50100 nm
Evident Technologies Luminescent biomarkers Semiconductor quantum dots with amine or carboxyl groups on the surface, emission from 350 to 2500 nm
Immunicon Tarcking and separation of different cell types magnetic core surrounded by a polymeric layer coated with antibodies for capturing cells
NanoCarrier Co., Ltd Drug delivery Micellar nanoparticles for encapsulation of drugs, proteins, DNA
Oxonica Ltd Sunscreens Doped transparent nanoparticles to effectively absorb harmful UV and convert it into heat
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Nanomaterials in the pharmaceutical pipeline
Dendrimers Drug delivery, imaging agents
VivaGel (SPL 7013) Fullerenes Drug delivery,
therapeutics Antioxidant fullerene Lipsomes
Drug delivery Doxil Superparamagnetic Drug
delivery, imaging Ferumoxitol particles
agents Ferumoxtran-10 , , Colloidal
gold particles Drug delivery, therapeutics
Aurimune, Aurothol Polymeric Nanoparticles
Drug delivery, therapeutics, Basulin,Contramid
imaging MRX-951 , Gold nanoshells
Photo-thermal tumour ablation
AuroLase Quantum dots Imaging, diagnostics
QDot-800 conjugate Self-assembling
peptide/protein particles Drug delivery,
therapeutics Abraxane
Marina A. Dobrovolskaia Scott E. McNeil Nature
Nanotech, vol2, 469, 2007
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Thank You