title: Synthesis, Photophysics and PDT Evaluation of Mono-, Di-, Tri- and Hexa-PEG Chlorins for Pointsource Photodynamic Therapy.
abstract: Pointsource photodynamic therapy (PSPDT) is a newly developed fiber optic method aimed at the delivery of photosensitizer, light and oxygen to a diseased site. Because of a need for developing photosensitizers with desirable properties for PSPDT, we have carried out a synthetic, photophysical and phototoxicity study on a series of PEGylated sensitizers. Chlorin and pheophorbide sensitizers were readily amenable to our synthetic PEGylation strategy to reach triPEG and hexaPEG galloyl pheophorbides and mono-, di-, triPEG chlorins. On screening these PEG sensitizers, we found that increasing the number of PEG groups, except for hexaPEGylation, increases phototoxicity. We found that three PEG groups but not less or more were optimal. Of the series tested, a triPEG gallyol pheophorbide and a triPEG chlorin were the most efficient at generating singlet oxygen, and produced the highest phototoxicity and lowest dark toxicity to Jurkat cells. A detailed kinetic analysis of the PEGylated sensitizers in solution and cell culture and media is also presented. The data provide us with steps in the development of PSPDT to add to the PDT tools we have in general.
authors.affiliation: Department of Physics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bornhütter
authors.affiliation: Department of Chemistry, Brooklyn College, Brooklyn, NY.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York City, NY.
authors.forename: Ashwini A
authors.initials: AA
authors.lastname: Ghogare
authors.affiliation: Department of Physics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Preuß
authors.affiliation: Department of Chemistry, Brooklyn College, Brooklyn, NY.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York City, NY.
authors.forename: Alexander
authors.initials: A
authors.lastname: Greer
authors.affiliation: Department of Physics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Röder
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002470:Cell Survival; D006801:Humans; D019169:Jurkat Cells; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D066244:Proton Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin