This research explores the limitations set by the local microenvironment in vivo on conventional photosensitizers that act via generation of toxic singlet oxygen. Hypoxia is a limiting factor to photodynamic therapy (PDT). Systematic determination of oxygen dependence of the photosensitizers will facilitate better understanding of in vivo photosensitization. Development of alternative, oxygen-independent photodamage sensitization mechanisms that overcome existing limitations in PDT is anticipated. The direct effects of the biological ri~iicroenvironment of the photosensitizer on its mechanism and efficiency will be determined, as well as i the effects of high local sensitizer concentration; direct reaction of photosensitizer intermediates with integral biomolecules and cellular localization sites on the photophysics and phototoxicity of photo-sensitizers will be determined in liposomes, erythrocyte ghosts and malignant cell suspensions. A general relationship will be constructed to predict efficacy of singlet oxygen photo sensitizers to cause cell damage. Diffuse reflectance laser flash photolysis will measure oxygen concentrations in vivo using oxygen-dependent triplet state kinetics. Measured 02 is combined with rate constants for natural decay and oxygen quenching of the triplet state to predict photosensitizer efficiency. This relationship will be tested using photosensitizers with different natural triplet lifetimes, varying 02 through N2 /02 gas mixtures and correlating observed phototoxicity with the efficiency predicted by the photophysical method. A third goal is to develop alternative oxygen-independent photo-sensitization mechanisms for photosensitized damage in biological media that overcome the limitations of hypoxia. Radical species, rather than singlet oxygen, will be generated through bond cleavage and photosensitization processes in related compounds. A correlation of reaction mechanisms with photoio'nization of normal and hypoxic cellular systems will ascertain the potential of radical-based strategies to effect oxygen-independent photodamage.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
United States
Zip Code
Lu, Yanyan; Jiang, Yan; Prokaeva, Tatiana et al. (2017) Oxidative Post-Translational Modifications of an Amyloidogenic Immunoglobulin Light Chain Protein. Int J Mass Spectrom 416:71-79
Sethi, Manveen K; Zaia, Joseph (2017) Extracellular matrix proteomics in schizophrenia and Alzheimer's disease. Anal Bioanal Chem 409:379-394
Hu, Han; Khatri, Kshitij; Zaia, Joseph (2017) Algorithms and design strategies towards automated glycoproteomics analysis. Mass Spectrom Rev 36:475-498
Pu, Yi; Ridgeway, Mark E; Glaskin, Rebecca S et al. (2016) Separation and Identification of Isomeric Glycans by Selected Accumulation-Trapped Ion Mobility Spectrometry-Electron Activated Dissociation Tandem Mass Spectrometry. Anal Chem 88:3440-3
Wang, Yun Hwa Walter; Meyer, Rosana D; Bondzie, Philip A et al. (2016) IGPR-1 Is Required for Endothelial Cell-Cell Adhesion and Barrier Function. J Mol Biol 428:5019-5033
Ji, Yuhuan; Bachschmid, Markus M; Costello, Catherine E et al. (2016) S- to N-Palmitoyl Transfer During Proteomic Sample Preparation. J Am Soc Mass Spectrom 27:677-85
Hu, Han; Khatri, Kshitij; Klein, Joshua et al. (2016) A review of methods for interpretation of glycopeptide tandem mass spectral data. Glycoconj J 33:285-96
Srinivasan, Srimathi; Chitalia, Vipul; Meyer, Rosana D et al. (2015) Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis 18:449-62
Yu, Xiang; Sargaeva, Nadezda P; Thompson, Christopher J et al. (2015) In-Source Decay Characterization of Isoaspartate and ?-Peptides. Int J Mass Spectrom 390:101-109
Steinhorn, Benjamin S; Loscalzo, Joseph; Michel, Thomas (2015) Nitroglycerin and Nitric Oxide--A Rondo of Themes in Cardiovascular Therapeutics. N Engl J Med 373:277-80

Showing the most recent 10 out of 253 publications