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Synthesis and in vitro PDT evaluation of new porphyrins containing meso ‐epoxymethylaryl cationic groups
Author(s) -
Carneiro Jaqueline,
Gonçalves Alan,
Zhou Zehua,
Griffin Kaitlin E.,
Kaufman Nichole E.M.,
Vicente Maria da Graça Henriques
Publication year - 2018
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.22824
Subject(s) - phototoxicity , cationic polymerization , singlet oxygen , photodynamic therapy , chemistry , porphyrin , photochemistry , photosensitizer , in vitro , context (archaeology) , combinatorial chemistry , oxygen , organic chemistry , biochemistry , paleontology , biology
Objectives Photodynamic therapy (PDT) is an effective cancer treatment that uses photosensitizers, light, and oxygen to destroy malignant cells. Porphyrins, and in particular the cationic derivatives, are the most investigated photosensitizers for PDT. In this context, it is important to study new methodologies to develop efficient cationic photosensitizers for use in PDT. Materials and Methods New porphyrins bearing cationic epoxymethylaryl groups were synthesized and characterized. Their cellular uptake, intracellular localization, and phototoxicity were evaluated in human HEp2 cells, and compared with their methylated analogs. Results All cationic porphyrins were efficient generators of singlet oxygen, with quantum yields in the range 0.35–0.61. The two methylated derivatives ( 3 and 4 ) accumulated the most within cells at all times investigated, up to 24 hours. Of these two porphyrins, 4 was the most phototoxic to the cells (LD 50 = 2.4 μM at 1.5 J/cm 2 ); however, porphyrin 3 also showed high phototoxicity (LD 50 = 7.4 μM at 1.5 J/cm 2 ). The epoxymethyl‐containing porphyrins were found to be less phototoxic than the methylated derivatives, with LD 50 > 38 μM. The neutral porphyrins showed no phototoxicity up to the 100 μM concentrations investigated, and had the lowest singlet oxygen quantum yields. All cationic porphyrins localized mainly in the cell ER, Golgi apparatus, and lysosomes. Conclusion Our results suggest that cationic methylated porphyrin derivatives are promising PDT photosensitizing agents. The epoxymethyl‐containing derivatives showed increased efficacy relative to the neutral analogs, and are good candidates for further investigation. Lasers Surg. Med. 50:566–575, 2018. © 2018 Wiley Periodicals, Inc.