Synthesis, Photophysics and PDT Evaluation of Mono‐, Di‐, Tri‐ and Hexa‐PEG Chlorins for Pointsource Photodynamic Therapy

• Published in: Photochemistry and photobiology Vol. 93; no. 5; pp. 1259 - 1268
• Main Authors: Bornhütter, Tobias, Ghogare, Ashwini A., Preuß, Annegret, Greer, Alexander, Röder, Beate
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.10.2017
• Subjects: Carbon-13 Magnetic Resonance Spectroscopy; Cell culture; Cell Survival; Fiber optics; Humans; Jurkat Cells; Optical fibers; Oxygen; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - therapeutic use; Phototoxicity; Polyethylene glycol; Porphyrins - chemical synthesis; Porphyrins - chemistry; Porphyrins - therapeutic use; Proton Magnetic Resonance Spectroscopy; Singlet oxygen; Spectrophotometry, Ultraviolet; Toxicity
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.12773

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. Sensitizers with three PEG groups but not less or more were found to be optimal for singlet oxygen generation and phototoxicity to Jurkat cells.