Many clinical examples exist which require the use of a high-precision technology to eradicate tumors that are located next to vital anatomical sites. Sites that are often inaccessible or unsafe for treatment by traditional surgical and medical methods include major blood vessels such as the carotid arteries, critical areas of the brain, and portions of the eye. We will develop a site-specific fiber optic-based singlet oxygen generator, which has the potential to be used as a precise photochemical surgical knife to destroy tumor cells in areas that require cytotoxic control and are inaccessible by surgical methods. A fiber optic-based singlet oxygen generator for targeted singlet oxygen delivery is proposed for use in photodynamic therapy and drug delivery. The objective is to design a heterogeneous photodynamic therapy device that uses the optical excitation of sensitizer molecules released from porous ends on hollow photonic band-gap optical fibers through which O2 flows. The proposed research is predicated upon our strong preliminary data showing that porous Vycor glass serves as a photosensitizer support and can be integrated to a hollow fiber optic that is effective in generating singlet oxygen in aqueous solution. The hypothesis is that sensitizer molecules released from the fiber optic device will be localized at a tumor site and that high concentrations of singlet oxygen will be produced for its destruction at that site. This project is innovative in that, to date, all photodynamic therapy strategies have involved the systemic administration of a sensitizer;our work would therefore be the first to cleave a photosensitizer from the end of a fiber optic device through which O2 flows. The improved singlet oxygen delivery and selectivity is expected to fill a new niche in preclinical photodynamic therapy.

Public Health Relevance

Problems exist in surgically removing tumors from complex sites, such as when tumors are directly adjacent to vital organs. A fiber optic-based device is proposed (for targeted delivery of cytotoxic singlet oxygen) for the potential application in diseases, such as brain tumors where exquisite precision is needed in the treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Enhancement Award (SC1)
Project #
5SC1GM093830-04
Application #
8474786
Study Section
Special Emphasis Panel (ZGM1-MBRS-X (CH))
Program Officer
Fabian, Miles
Project Start
2010-07-21
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$374,975
Indirect Cost
$136,137
Name
Brooklyn College
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
620127691
City
New York
State
NY
Country
United States
Zip Code
11210
Mahendran, Adaickapillai; Ghogare, Ashwini A; Bittman, Robert et al. (2016) Synthesis and antiproliferative properties of a new ceramide analog of varacin. Chem Phys Lipids 194:165-70
Ghogare, Ashwini A; Miller, Joann M; Mondal, Bikash et al. (2016) Fluorinated Photodynamic Therapy Device Tips and their Resistance to Fouling for In Vivo Sensitizer Release. Photochem Photobiol 92:166-72
Oliveira, Marilene Silva; Ghogare, Ashwini A; Abramova, Inna et al. (2015) Mechanism of Photochemical O-Atom Exchange in Nitrosamines with Molecular Oxygen. J Org Chem 80:6119-27
Malek, Belaid; Ghogare, Ashwini A; Choudhury, Rajib et al. (2015) Air-Water Interface Effects on the Regioselectivity of Singlet Oxygenations of a Trisubstituted Alkene. Tetrahedron Lett 56:4505-4508
Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A et al. (2015) Photoactive fluoropolymer surfaces that release sensitizer drug molecules. J Phys Chem B 119:4155-64
Zhao, Yuanyuan; Liu, Yang; Xu, Qianfeng et al. (2014) Singlet oxygen generation on porous superhydrophobic surfaces: effect of gas flow and sensitizer wetting on trapping efficiency. J Phys Chem A 118:10364-71
Choudhury, Rajib; Greer, Alexander (2014) Synergism between airborne singlet oxygen and a trisubstituted olefin sulfonate for the inactivation of bacteria. Langmuir 30:3599-605
Rudshteyn, Benjamin; Castillo, Alvaro; Ghogare, Ashwini A et al. (2014) Theoretical study of the reaction formalhydrazone with singlet oxygen. Fragmentation of the C=N bond, ene reaction and other processes. Photochem Photobiol 90:431-8
Walalawela, Niluksha; Greer, Alexander (2014) Photoactive chitosan: a step toward a green strategy for pollutant degradation. Photochem Photobiol 90:1216-8
Ghogare, Ashwini A; Rizvi, Imran; Hasan, Tayyaba et al. (2014) ""Pointsource"" delivery of a photosensitizer drug and singlet oxygen: eradication of glioma cells in vitro. Photochem Photobiol 90:1119-25

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