2026-04-17T10:25:30Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/74442026-02-06T12:53:36Zcom_10259_4363com_10259_5086com_10259_2604com_10259_3924com_10259.4_2516com_10259_3592com_10259_3591com_10259.4_106col_10259_4364col_10259_3925col_10259.4_2517col_10259_3930

00925njm 22002777a 4500 dc Echevarría Poza, Igor author Zafon, Elisenda author Barrabés, Sílvia author Martínez, María Ángeles author Ramos Gómez, Sonia author Ortega Santamaría, Natividad author Manzano, Blanca R. author Jalón Sotés, Félix Ángel author Quesada Pato, Roberto author Espino Ordóñez, Gustavo author Massaguer Vall-Llovera, Anna author 2022-06 Despite their outstanding properties as potential photosensitizers for photodynamic therapy (PDT), Ir(III) biscyclometalated complexes need both further developments to overcome remaining limitations and in-depth investigations into their mechanisms of action to reach clinic application in the treatment of cancer. This work describes the synthesis of a family of Ir(III) complexes of general formula [Ir(C^N)2(N^N′ )]Cl (N^N′ = thiabendazole-based ligands; C^N = ppy (2-phenylpyridinate) (Series A), or dfppy (2-(2,4-difluorophenyl)pyridinate) (Series B)) and their evaluation as potential PDT agents. These complexes are partially soluble in water and exhibit cytotoxic activity in the absence of light irradiation versus several cancer cell lines. Furthermore, the cytotoxic activity of derivatives of Series A is enhanced upon irradiation, particularly for complexes [1a]Cl and [3a]Cl, which show phototoxicity indexes (PI) above 20. Endocytosis was established as the uptake mechanism for [1a]Cl and [3a]Cl in prostate cancer cells by flow cytometry. These derivatives mainly accumulate in the mitochondria as shown by colocalization confocal microscopy experiments. Presumably, [1a]Cl and [3a]Cl induce death on cancer cells under irradiation through apoptosis triggered by a multimodal mechanism of action, which likely involves damage over mitochondrial DNA and mitochondrial membrane depolarization. Both processes seem to be the result of photocatalytic oxidation processes. 0162-0134 http://hdl.handle.net/10259/7444 10.1016/j.jinorgbio.2022.111790 Photodynamic therapy Iridium Cyclometalated complexes Cancer Mitochondria DNA Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer