Nanomedicine

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Nanomedicine

• A vision for future health, utilizing
  cross-fertilization of nanotechnology and biology
  to produce novel approaches
• for probing biological processes at the
  molecular, subcellular and cellular levels.
• For sensing and bioimaging of biological events
• For incorporating multimodal diagnostics
• For implementing effective and safe targeted gene
  therapy

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• NANOPHOTONICS AND NANOMEDICINE
• Control of Optical Transitions
• Quantum Dots for Bioimaging
• Novel Optical Resources
• Rare-earth up-converters for bioimaging
• Plasmonic nanoparticles for biosensing or therapy
• Nanocontrol of Excitation Dynamics
• Nanoscopic sub-cellular interactions using FRET
• Nonlinear optical techniques for bioimaging and
  light-activated therapy
• Manipulation of Light Propagation
• Biosensing using photonic crystals
• Nanoscopic Field Enhancement
• Plasmonic enhancement for apertureless near field
• Plasmonic enhancement for Raman and fluorescence

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Multimodal Imaging



H
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Fluorescent dye
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i

Fe3O4 nanoparticle
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H
50 µm

C
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H

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Enhanced Contrast MRI
In vivo fluorescence imaging
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ORMOSIL
Tumor site
HPPH
Enhanced image
2
Enhance
Fluorenscence
Image
Targeting
Agent
Enhanced MRI
Contrast for Cancer
Imaging for Drug
And Therapeutic
Action
NANOMEDICINE
Nanotechnology in
Biomedical Systems
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Photodynamic Therapy
hn
O2
Porphyrin Porphyrin O2
singlet
( Localizes and accumulates at tumor sites )
Destroys Cancerous Cells
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Bifunctional Chromophores for Photodynamic
Therapy. Real time monitoring of drug
distribution, localization and activation.
Photosensitizer
Fluorophore for imaging

• Conditions
• Photosensitizer absorbs at a shorter wavelength
  than the fluorophore
• No significal energy transfer from the
  photosensitizer to the fluorophore
• At the excitation of fluorophore no photodynamic
  therapeutic action.

Collaboration Dr. R. Pandey, Roswell Park Cancer
Institute
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Studies of PDT efficacy in vitro and uptake of
the conjugate in vivo
Dr. R. Pandey, Roswell Park Cancer Institute
Cell viability study
Excitation of photosensitizer chromophore (665
nm), PDT effect
Excitation of cyanine fluorophore (810 nm), No
PDT effect
Distribution of 5 in various organ parts at (A)
48 and (B) 72 h post injection from RIF tumor
bearing mice imaging by fluorescence from
cyanine fluorophore
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Two- Photon Photodynamic Therapy
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Two-photon dendrimer-photosensitizer for
photodynamic therapy
In collaboration with Frechet Research Group
University of California, Berkeley
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(No Transcript)
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• NANOPARTICLE PLATFORM FOR PHOTODYNAMIC THERAPY
•   Co-localization to Control Excitation Dynamics
•   Up-conversion Photodynamics Therapy
•   Multimodal Imaging Capability
•   Added Targeting
•   Enhanced Biodistribution

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Organically Modified Silica (ORMOSIL) Nanoclinic
Encapsulating Hydrophobic Drugs for Diagnostic
Imaging and PDT
Schematic of HPPH doped ORMOSIL Nanoclinic
TEM image of HPPH doped ORMOSIL nanoparticles
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HPPH-ORMOSIL Nanoparticles
KB Cells
Transmission and Fluorescence Images HPPH-ORMOSIL
nanoparticles cells and tissue
Human Tumor tissue
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Collocalization of a photosensitizer with heavy
atom
I
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I2
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I2
I2
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I2
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ORMOSIL nanoparticle with coencapsulated
photosensitiser HPPH and I2 Nanoparticle shell
can be modified by insertion of I.
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I2 inside nanoparticles influences on the
absorption and emission of HPPH
1O2 generation by HPPH manifested by 1O2
phosphorescence
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• Gene Therapy
• Diseases (short list)
• Diabetes,
• Cystic fibrosis,
• Cancers (pancreatic, breast, prostrate, etc),
• Parkinsons Disease
• Problems
• Genetic material susceptible to enviromental
  degradation
• Lack of effective in vivo delivery system.
• Viral based systems have not adequately provided
  answer.
• Solutions (non-viral based delivery systems)
• Liposomes
• Organic based particles (PEG, dextran, chitose,
  etc)
• Inorganic nanoparticles
• Silica based nanoparticles

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Optically Trackable ORMOSIL Nanoparticles for
Gene Delivery
FRET experiments
Encapsulated fluorescent dye And-10 (labs 400
nm, lem 461 nm), DONOR
DNA stained with YOYO-1 (labs 491 nm, lem
509 nm) ACCEPTOR
hn
hn
FRET
hn
20 nm
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In Vitro Uptake and Transfection of Cells by
ORMOSIL/DNA Nanoparticles
eGFP expression
DNA delivered into cell nuclei
Expression of eGFP in cells transfected with eGFP
ORMOSIL nanoparticles vector
Cellular Uptake of DNA loaded ORMOSIL
nanoparticles and subsequent translocation of DNA
into the nucleus of the cell
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In Vivo Transfection of Neuron
A
B
Transfection of neurons in Substantia Nigra of
mouse brain (plate A) with ORMOSIL-pEGFP. EGFP
(green) is expressed in tyrosine hydroxylase
immunopositive (red) dopamine neuron (plate B).
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Opportunities in Nanophotonics




Dendritic Structures for Up
-
conversion Lasing, Optical
Limiting and Electro
-
optic



Quantum
-
Engineering of Heirarchiacal Nanostructures
(Quantum Dot
-
Quantum Well, Multiple Shells)



Nanocontrol of Dynamics of Carrier Transport and
Excitation
Tran
sport



Quantum Confined Semi
-
Conductor Polymner
Nanocomposties for Solar Cells and LEDs



Novel Supramolecular Templates for Self
-
Assemblying of
Nanostructures



Photonic Crystals Based Microcavities and Optical
Circuitry



Photonically Directed Metallic Nanostr
uctures



Molecular Electronics
with
Three
Terminal
Molecule
s

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Opportunities in Biophotonics

• In vivo Bioimaging, Spectroscopy, and Optical
  Biopsy
• Nano-Biophotonic Probes (Nanofluorophores)
• Single Molecule Biofunctions
• Multiphoton Processes for Biotechnology
• Real-Time Monitoring of Drug Interactions
• Nanomedicine

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Acknowledgements

• Researchers at the Institute
• Prof. E. Bergey
• Prof. A. Cartwright
• Prof. M. Swihart
• Prof. E. Furlani
• Dr. A. Kachynski
• Dr. A. Kuzmin
• Dr. Y. Sahoo
• Dr. H. Pudavar
• Dr. T. Ohulchanskyy
• Dr. D. Bharali
• Dr. D. Lucey
• Dr. K. Baba
• Dr. J. Liu

• Outside Collaborators
• Prof. R.Boyd
• Prof. J.Haus
• Prof. J M J Frechet
• Prof. M. Stachowiak
• Dr. A. Oseroff
• Dr. R. Pandey
• Dr. J. Morgan
• Dr. P Dandona

• DURINT/AFSOR
• Dr. Charles Lee

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Lighting the Way to Technology through
Innovation

• The Institute for Lasers, Photonics and
  Biophotonics
• University at Buffalo
• Emerging Opportunities in Nanophotonics and
  Biophotonics

www.biophotonics.buffalo.edu