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Nanomedicine

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

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Nanomedicine

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  1. 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

  2. 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

  3. C O O H H O O C O H H O C O O H H O O C C O O H H O O C C O O H C O O H O O C C C C C O O O O O O O O H H H H O O O O H H H H H H H H O O O O O O O O C C C C C C C C O O O O O O O O H H H H Multimodal Imaging H O O C O H H O Fluorescent dye H H O O C C O O H i Fe3O4 nanoparticle H O O C O H H O O O H H O O C H O O C C O O H 50 µm C O O H H O O C C O O H H O O C O H C O O H O H H O O C C O O H Enhanced Contrast MRI In vivo fluorescence imaging

  4. Labeled Brain Tumor Enhanced In Vivo 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

  5. Photodynamic Therapy hn O2 Porphyrin Porphyrin + O2 singlet ( Localizes and accumulates at tumor sites ) Destroys Cancerous Cells

  6. O C H 6 1 3 H C C H 3 3 H C C H C H 3 2 5 3 N H N H N N H C C H 3 3 O H N C O c c P P P P S C H = C H C H C H N + N C H O C H O 2 2 - C H C H C H S O C H C H C H S O N a 2 2 2 2 2 2 O O 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

  7. Dr. R. Pandey, Roswell Park Cancer Institute Studies of PDT efficacy in vitro and uptake of the conjugate in vivo 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

  8. 2 hn + Porphyrin Porphyrin + Dye Dye+ Energy transfer ( Two photon absorption of light from a pulsed laser at 800 nm) O2 O2 singlet Destroys Cancerous Cells Advantages of Up-Conversion Therapy 1. Deeper tissue penetration 2. Less collateral tissue damage 3. More Precision Two- Photon Photodynamic Therapy

  9. Two-photon dendrimer-photosensitizer for photodynamic therapy 1. IR Excitation (TPA) S S N N 2. Energy Transfer to Porphyrin N N O O S S N N O O N N O O O O N NH N NH O O O O N N O O N N S S O O N N 3. Singlet O2 Generation 1O 3O N N S S In collaboration with Frechet Research Group University of California, Berkeley

  10. NANOPARTICLE PLATFORM FOR PHOTODYNAMIC THERAPY • Co-localization to Control Excitation Dynamics •   Up-conversion Photodynamics Therapy •   Multimodal Imaging Capability •   Added Targeting •   Enhanced Biodistribution

  11. ORMOSIL Shell HPPH HPPH SiO2 ORMOSIL Targeting Agent 20-50 nm 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

  12. 100 80 60 % Cell-survival 40 20 0 Blank Tween-80 HPPH/Tween-80 Blank Nanoparticles HPPH/Nanoparticles Singlet Oxygen Generation In Vitro Cytotoxic Effect HPPH-ORMOSIL Nanoparticles KB Cells Transmission and Fluorescence Images HPPH-ORMOSIL nanoparticles cells and tissue Human Tumor tissue

  13. External heavy atom effect Enhanced Intersystem Crossing Enhanced Singlet Oxygen Generation Collocalization of a photosensitizer with heavy atom I I I I2 I I I I2 I2 I I I2 I I I I I ORMOSIL nanoparticle with coencapsulated photosensitiser HPPH and I2 Nanoparticle shell can be modified by insertion of I.

  14. I2 inside nanoparticles influences on the absorption and emission of HPPH 1O2generation by HPPH manifested by 1O2 phosphorescence

  15. Gene Therapy • Diseases (short list) • Diabetes, • Cystic fibrosis, • Cancers (pancreatic, breast, prostrate, etc), • Parkinson’s 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

  16. 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

  17. 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

  18. 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).

  19. 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

  20. 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

  21. 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

  22. “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

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