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. Multimodal Imaging 50 µm Fe 3 O 4 nanoparticle Fluorescent dye Enhanced Contrast MRI In vivo fluorescence imaging H HO COOH HOO HOOC OH COOH HOOC HOOC OH HOOC COOH HOOC OH COOH HOOC HOOC OH COOH COOH HOOC OH i

4. Enhanced MRI Contrast for CancerEnhanced In Vivo Imaging for Drug And TherapeuticAction NANOMEDICINE: Nanotechnology in Biomedical Systems 2 Targeting Agent HPPH ORMOSIL Tumor site: Enhanced image Labeled Brain Tumor EnhanceFluorenscenceImage

5. Photodynamic Therapy Porphyrin Porphyrin + O 2 singlet h O2O2 ( Localizes and accumulates at tumor sites ) Destroys Cancerous Cells

6. Bifunctional Chromophores for Photodynamic Therapy. Real time monitoring of drug distribution, localization and activation. 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 Fluorophore for imaging Photosensitizer

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

8. Two- Photon Photodynamic Therapy ( Two photon absorption of light from a pulsed laser at 800 nm) 2 h O2O2 Destroys Cancerous Cells DyeDye + O 2 singlet Porphyrin + Energy transfer + Porphyrin Advantages of Up-Conversion Therapy 1. Deeper tissue penetration 2. Less collateral tissue damage 3. More Precision

9. In collaboration with Frechet Research Group University of California, Berkeley Two-photon dendrimer-photosensitizer for photodynamic therapy

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

12. Organically Modified Silica (ORMOSIL) Nanoclinic Encapsulating Hydrophobic Drugs for Diagnostic Imaging and PDT TEM image of HPPH doped ORMOSIL nanoparticles HPPH ORMOSIL Shell SiO 2 20-50 nm Targeting Agent HPPH ORMOSIL Schematic of HPPH doped ORMOSIL Nanoclinic

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

14. Collocalization of a photosensitizer with heavy atom External heavy atom effect Enhanced Intersystem Crossing Enhanced Singlet Oxygen Generation ORMOSIL nanoparticle with coencapsulated photosensitiser HPPH and I 2 Nanoparticle shell can be modified by insertion of I. I2I2 I2I2 I2I2 I2I2 I I I I I I I I I I I I I

15. I 2 inside nanoparticles influences on the absorption and emission of HPPH 1 O 2 generation by HPPH manifested by 1 O 2 phosphorescence

16. 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

17. FRET experiments Encapsulated fluorescent dye And-10 ( abs = 400 nm, em = 461 nm), DONOR h ‘ h ‘’ FRET h ‘’’ DNA stained with YOYO-1 ( abs = 491 nm, em = 509 nm) ACCEPTOR ~ 20 nm Optically Trackable ORMOSIL Nanoparticles for Gene Delivery

18. Cellular Uptake of DNA loaded ORMOSIL nanoparticles and subsequent translocation of DNA into the nucleus of the cell In Vitro Uptake and Transfection of Cells by ORMOSIL/DNA Nanoparticles Expression of eGFP in cells transfected with eGFP ORMOSIL nanoparticles vector DNA delivered into cell nuclei eGFP expression

19. 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). In Vivo Transfection of Neuron A B

20. 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 Transport  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 Nanostructures  Molecular Electronicswith ThreeTerminal Molecules

21. 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 Opportunities in Biophotonics

22. 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 DURINT/AFSOR  Dr. Charles Lee 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

23. “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