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  • 1. Integrated Fluorescent, Radio-Opaque and Magnetic Nanoparticles for Intra-Arterial Pre-Operative Brain Mapping and Broad Based Diagnostic Imaging Swadeshmukul Santra Department of Neurological Surgery and Particle Engineering Research Center University of Florida, PO Box 100265, Gainesville, FL 32610 Phone: (352) 846-1194 Fax: (352) 846-1196 Track 2 - Convergence of Biotechnology and Nanotechnology Novel fluorescent, radio-opaque and magnetic nanoparticles are being developed for intra-arterial pre-operative brain mapping and broad based in vivo diagnostic imaging. A unique synthesis route has been employed to produce monodisperse and ultrasmall (<10 nm) nanoparticle probes (NPs). These probes will stand out from conventional fluorescent dyes because of their remarkable photostability, brightness and suitability for in vivo multifaceted bioimaging (fluorescence, CT scan/angiography, MR imaging/angiography). Two immediate medical applications are: (i) endovascular pre- operative brain mapping and (ii) diagnostic NPs for metastatic adenocarcinoma. Endovascular pre-operative brain mapping technique will produce a visual contrast between eloquent (functional) and non-eloquent (“silent”) brain tissue. The significance of this approach is to individualize the unique brain functional map of each patient requiring brain resection to improve their neurosurgical outcome. This technique will be useful for malignant glioma resection, low-grade glioma resection, arteriovenous malformation (AVM) resection, brain resection for epilepsy surgery, and other functional neurosurgical resections. It will improve upon current techniques by allowing a precise, direct, real-time visualization of non-eloquent/silent brain tissue that can be resected with absolute assurance that no neurological deficit will result from the neurosurgical resection. For diagnosis of metastatic adenocarcinoma, NP tracers will not only allow surgeons to get CT/MRI scans non-invasively but also will guide them for effective resection of lesions in real time through NP fluorescence. The research outcome will have two innovative deliverable endpoints-robust formulations for in vivo imaging of malignant tumors and neurologically non-functional brain tissues; and a robust technique for neurosurgeons for effective surgical treatment of brain tumors, epilepsy and AVMs. We believe that this cutting-edge interdisciplinary research thrust will aid in the fulfillment of National Nanotechnology Initiative (NNI) and will promote medical application oriented nanobiotechnology research. Contrast agents have a market value of over a billion dollars, with MRI growing to US $0.5 billion per year. More than 18 million radiology, 3 million diagnostic and interventional cardiology, and 11 million cardiac ultrasound procedures are performed in the United States each year. The worldwide market for x-ray contrast agents alone now totals about US $2 billion annually. The proposed NPs are designed for multifaced
  • 2. bioimaging. Angiography, CT-scan, MRI scan, and fluorescence imaging, all can be performed using our state-of-the-art in vivo tracers. We anticipate that the market size for these NPs will be at least US $1 billion annually.
  • 3. Curriculum Vitae – Swadeshmukul Santra CONTACT INFORMATION Department of Neurological Surgery and Particle Engineering Research Center University of Florida, PO Box 100265, Gainesville, FL 32610 Phone: (352) 846-1194, Fax: (352) 846-1196 Email: santra@neurosurgery.ufl.edu Website: http://www.neurosurgery.ufl.edu/FacultyPage/santra.html HIGHER EDUCATION 1993 – 1998 Indian Institute of Technology Kanpur, Kanpur, India PhD in Chemistry 1990 – 1992 University of Kalyani, West Bengal, India MSc in Physical Chemistry 1987 – 1990 Vidyasagar University (Tamluk College), West Bengal, India BSc in Chemistry EMPLOYMENT HISTORY University of Florida Department of Neurological Surgery and Particle Engineering Research Center (PERC) Research Assistant Professor: January, 2004- Present. University of Florida Department of Neurological Surgery Research Assistant Professor: September, 2002- January, 2004. University of Florida Department of Materials Science and Engineering Post doctoral Research Associate in Materials Chemistry/Microfabritech: Nov 2000 – Sept. 2002. University of Florida Department of Chemistry Post Doctoral Research Associate in Bioanalytical Chemistry/Biotechnology: Nov 1998 – Nov. 2000. AWARDS & PROFESSIONAL ACTIVITIES • Research Fellowship, Indian Institute of Technology Kanpur, India • Research Fellowship, Council of Scientific and Industrial Research, India • Member- American Chemical Society • Reviewer for journals:
  • 4. (i) Spectrochimica Acta Part A (Elsevier Science B.V.) (ii) Journal of Photochemistry and Photobiology A: Chemistry (Elsevier Science B.V.) (iii) Journal of Biomedical Optics (SPIE) (iv) Journal of Physical Chemistry (ACS) (v) Langmuir (ACS) (vi) Analyst (Royal Society of Chemistry, UK) (vii) Chemical Communications (Royal Society of Chemistry, UK) (viii) Physical Chemistry Chemical Physics ONGOING PROJECTS 1. Development of fluorescent nanoparticles for multifaceted bioimaging 2. Development of fluorescent brain mapping formulations 3. Development of highly sensitive fluorescent nanoparticles for stroke biomarker detection 4. Confocal study for the assessment of cell-nanoparticle interaction 5. Endovascular microstent-graft coverings for treatment of intracranial aneurysms and intracranial arteriovenous fistulas 6. Development of non-metallic polymer stent-graft for the treatment of intracranial aneurysms and intracranial arteriovenous fistulas 7. Development of mechanical thrombectomy microdevices for the treatment of ischemic stroke PATENTS 1. Mericle RA, Batich CD, Watkins CS, Burry MV, Richter OE, Santra S “Method of endovascular brain mapping”, US Patent Pending (Application # 20030236457), 2003. 2. Santra S, Mericle RA, Batich CD, Eskioglu E and Stanley, JT, “Apparatus and Methods for Disruption and Removal of Luminal Occlusions”, US Patent Pending (Univ. of Florida Reference # 11059), 2003. 3. Mericle RA, Santra S and Batich CD. Polymeric Reconstrainable, Repositionable, Detachable, Percutaneous Endovascular Stent-Graft Mixture Technology. US Patent pending (Univ. of Florida Reference # 10915), 2002. 4. Mericle RA, Santra S, Burry MV, Watkins CS and Batich CD, “Tubular polymer stent coverings” US Patent pending (Univ. of Florida Reference # 10933), 2002. 5. Batich CD, Eadens M, Santra S, Leamy P, Burry MV, Watkins CS, Mericle RA, “Biodegradable embolic agents as drug delivery methods” US Patent pending (Univ. of Florida Reference # 10926), 2002. 6. Tan W, Santra S, Peng Z, Tapec R, Dobson J, “Method for identifying cells”, US Patent Pending (Application No. 20020098529), 2002. 7. Tan W, Santra S, Peng Z, Tapec R, Dobson J, “Coated nanoparticles”, US Patent # 6,548,264. PUBLICATION
  • 5. 1. Santra S, Moloye O, Thula T, Liesenfeld B, Vicens M, Wang L, Batich CD, Tan W and Mericle RA. Do BALB/3T3 fibroblast cells overexpress folate receptors? A fluorescence confocal study with folate immobilized fluorescent silica nanoparticles CHEM COMM 2004 (under revision) 2. Santra S, Liesenfeld B, Chatel D, D. Batich CD, Cao Z, Tan W and Mericle RA. Development of novel folate immobilized fluorescent silica nanoparticles for sensitive detection of folate receptors in neoplastic cells J NANOSCI NANOTECHNO 2004 (under revision) 3. Santra S, Bagwe RP, Jessie T. Stanley JT, Watkins CS, Tan W and Mericle RA Development of novel fluorescent, radio-opaque and MRI active silica nanoparticles for multifaceted bioimaging CHEM COMM 2004 (under revision) 4. Gu L, Santra S, Mericle RA and Kumar AV Finite element analysis of covered microstents J BIOMECH 2004 (under revision) 5. Santra S, Holloway P, Batich CD Fabrication and testing of a magnetically actuated micropump SENSORS AND ACTUATORS B: CHEM, 87 (2): 358-364 Dec 10 2002. 6. Santra S, Zhang P, Wang KM, Tapec R, Tan WH Conjugation of biomolecules with luminophore-doped silica nanoparticles for photostable biomarkers ANAL CHEM 73 (20): 4988-4993 OCT 15 2001. 7. Monde Q, Santra S, Zhang P, Tan WH Biochemically functionalized silica nanoparticles ANALYST 126 (8): 1274-1278 AUG 2001. 8. Santra S, Tapec R, Theodoropoulou N, Dobson J, Hebard A, Tan WH Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: The effect of nonionic surfactants LANGMUIR 17 (10): 2900-2906 MAY 15 2001. 9. Santra S, Wang KM. Tapec, R. U., Tan WH Development of novel dye-doped silica nanoparticles for biomarker application J BIOMED OPT 6 (2): 160-166 APR 2001. 10. Santra S, Krishnamoorthy G, Dogra SK Spectral characteristics of the methylated derivatives of 2-(2 '-aminophenyl) benzimidazole: effects of solvents J MOL STRUCT 559 (1-3): 25-39 JAN 7 2001. 11. Fang X, Schuster S, Liu X, Correll T, Zhang P, Tapec R, Santra S, Qhobosheanne M, Lou JH and Tan WH Molecular beacon biosensors for DNA /RNA analysis in "Advances in Nucleic Acid and Protein
  • 6. Analyses, Manipulation and Sequencing", SPIE, (Patrick Limbach, John Owicki, Ramesh Raghavachari and Weihong Tan, Editors), 2000, 3926, 2-8. 12. Santra S, Zhang, P, Tan WH Novel interaction between glutamate and the Cu2+/DMABN/b -CD complex J PHYS CHEM A 104 (51): 12021-12028 DEC 28 2000. 13. Santra S, Dogra SK Excited state intramolecular proton transfer in the anionic species of 2-(2'- acetamidophenyl)bezimidazole in the aqueous medium CHEM PHYS LETT 327: (3-4) 230-237 SEP 8 2000. 14. Santra S, Dogra SK Effect of micelles on the spectral characteristics of the prototropic species of 2-(2'- aminophenyl)benzimidazole SPECTROCHIM ACTA A 56: (5) 915-925 APR 2000. 15. Santra S, Krishnamoorthy G, Dogra SK Excited state intramolecular proton transfer in 2-(2'-acetamidophenyl) benzimidazole J PHYS CHEM A 104: (3) 476-482 JAN 27 2000. 16. Santra S, Zhang P, Tan WH The restoration of pyrene fluorescence of a Cu-II-beta-cyclodextrin-pyrene complex CHEM COMMUN (14) 1301-1302 JUL 21 1999. 17. Santra S, Krishnamoorthy G, Dogra SK Excited state intramolecular proton transfer in 2-(2'-benzamidophenyl) benzimidazole: effect of solvents CHEM PHYS LETT 311: (1-2) 55-61, 1999. 18. Santra S, Dogra SK Prototropism of the methylated derivatives of 2-(2'-aminophenyl) benzimidazole J LUMIN 81: (4) 249-262, 1999. 19. Santra S, Dogra SK Spectral characteristics of the monocations of 2-(2'-aminophenyl)benzimidazole in different solvents J MOL STRUCT 478: (1-3) 169-183, 1999. 20. Saha SK, Santra S, Dogra SK Prototropic equilibrium of 2-aminofluorene in non-ionic micelles: Tweens J MOL STRUCT 478: (1-3) 199-210, 1999. 21. Santra S, Dogra SK Excited state intramolecular proton transfer in 2-(2'-N-palmitoyl-aminophenyl)benzimidazole: effect of carbonyl group J MOL STRUCT 476: (1-3) 223-233, 1999. 22. Santra S, Dogra SK Excited state intramolecular proton transfer in 2-(2 '-aminophenyl) benzimidazole in micelles J PHOTOCHEM PHOTOBIOL A 115: (3) 249-256, 1998.
  • 7. 23. Santra S, Dogra SK Excited-state intramolecular proton transfer in 2-(2'-aminophenyl) benzimidazole CHEM PHYS 226: (3) 285-296, 1998. 24. Santra S, Dogra SK Solvatochromism and prototropic reactions of 2-quinoxalinone (vol 207, pg 103, 1996) CHEM PHYS 226: (1-2) 229-229, 1998. 25. Santra S, Dogra SK Spectral characteristics of 2-(2'-aminophenyl)benzimidazole in beta-cyclodextrin J PHOTOCHEM PHOTOBIOL A 101: (2-3) 221-227, 1996. 26. Santra S, Dogra SK Solvatochromism and prototropic reactions of 2-quinoxalinone CHEM PHYS 207: (1) 103-113, 1996. PRESENTATION Santra S, Bagwe RP, Tan WH, Watkins CS, Stanley JT, Mericle RA. “A novel synthesis of fluorescent, radio-opaque, paramagnetic silica nanoparticles for multifaceted bioimaging applications” PITTCON 2004, Chicago, IL (accepted for oral presentation) Santra S, Eskioglu E, Burry MV, Watkins CS, Stanley JT, Mericle RA “Development of TAT (a cell penetrating peptide) conjugated fluorescent nanoparticles for preoperative intra-arterial brain mapping” 2004 AANS (American Association of Neurological Surgeons) annual meeting, Orlando, FL (accepted for oral presentation) Liesenfeld B, Chatel D, Rau-Zink C, Santra S, Batich CD, Mericle RA “Folate conjugated FITC-doped silica nanoparticles for cancer detection” PITTCON 2004, Chicago, IL (accepted for oral presentation) Eskioglu E, Burry MV, Stanley JT, Watkins CS, Santra S and Mericle RA “New Zealand White Rabbit Kidney Stroke Model for Mechanical Thrombolysis” 2004 AANS Annual Meeting, San Diego, CA (accepted for oral presentation). Gu L, Santra S, Mericle RA, Kumar AV “Covered microstent for the treatment of intracranial wide-necked and fusiform aneurysms: A finite element analysis for the design of stent coverings”, 2003 Summer Bioengineering Conference, June 25- 29, 2003, Sonesta Beach Resort in Key Biscayne, Florida. Bagwe RP, Santra S, Tan WH “Effect of particle size and reaction conditions on optical properties of TMR-dextran doped silica nanoparticles”, PITTCON 2003, Orlando, FL. Bradman N, Santra S, Davidson M, Holloway PH “Modes of failure in an artificial eyelid”, Joint Symposium Florida AVS Science and Technology Society Florida Society for Microscopy, 2002, Orlando, FL.
  • 8. Santra S, Zhang P, Qhobosheane, M, Tapec, R. U., Tan WH, “Silica based nanoparticles”, Oral presentation in First Georgia Tech Conference in Nanoscience and Nanotechnology, 2000, Atlanta, GA. Santra S, Tan WH. Oral presentation in SIS-2000 (Surfactants in solutions) Symposium, 2000 at Gainesville, FL. Santra S, Tan WH. Oral presentation in ACS (American Chemical Society) meeting, 1999, Orlando, FL. Santra S, Dogra SK, poster presentation at TSRP'98 (international symposium), Bhabha Atomic Research Centre (BARC), Trombay, Mumbai.