title: Synthesis and in vitro biological evaluation of lipophilic cation conjugated photosensitizers for targeting mitochondria.
abstract: Mitochondria-specific photosensitizers were designed by taking advantage of the preferential localization of delocalized lipophilic cations (DLCs) in mitochondria. Three DLC-porphyrin conjugates: CMP-Rh (a core modified porphyrin-rhodamine B cation), CMP-tPP (a core modified porphyrin-mono-triphenyl phosphonium cation), CMP-(tPP)(2) (a core modified porphyrin-di-tPP cation) were prepared. The conjugates were synthesized by conjugating a monohydroxy core modified porphyrin (CMP-OH) to rhodamine B (Rh B), or either one or two tPPs, respectively, via a saturated hydrocarbon linker. Their ability for delivering photosensitizers to mitochondria was evaluated using dual staining fluorescence microscopy. In addition, to evaluate the efficiency of the conjugates as photosensitizers, their photophysical properties and in vitro biological activities were studied in comparison to those of CMP-OH. Fluorescence imaging study suggested that CMP-Rh specifically localized in mitochondria. On the other hand, CMP-tPP and CMP-(tPP)(2) showed less significant mitochondrial localization. All conjugates were capable of generating singlet oxygen at rates comparable to CMP-OH. Interestingly, all cationic conjugates showed dramatic increase in cellular uptake and phototoxicity compared to CMP-OH. This improved photodynamic activity might be primarily due to an enhanced cellular uptake. Our study suggests that Rh B cationic group is better at least for CMP than tPP as a mitochondrial targeting vector.
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Rajaputra
authors.forename: Gregory
authors.initials: G
authors.lastname: Nkepang
authors.forename: Ryan
authors.initials: R
authors.lastname: Watley
authors.forename: Youngjae
authors.initials: Y
authors.lastname: You
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004735:Energy Transfer; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D012235:Rhodamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D002412:Cations; D017319:Photosensitizing Agents; D011166:Porphyrins; D012235:Rhodamines; D026082:Singlet Oxygen; C029773:rhodamine B