RT info:eu-repo/semantics/article
T1 Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer
A1 Echevarría Poza, Igor
A1 Zafon, Elisenda
A1 Barrabés, Sílvia
A1 Martínez, María Ángeles
A1 Ramos Gómez, Sonia
A1 Ortega Santamaría, Natividad
A1 Manzano, Blanca R.
A1 Jalón, Félix A.
A1 Quesada Pato, Roberto
A1 Espino Ordóñez, Gustavo
A1 Massaguer, Anna
K1 Photodynamic therapy
K1 Iridium
K1 Cyclometalated complexes
K1 Cancer
K1 Mitochondria
K1 DNA
K1 Química orgánica
K1 Chemistry, Organic
K1 Química analítica
K1 Chemistry, Analytic
K1 Química inorgánica
K1 Chemistry, Inorganic
K1 Medicina
K1 Medicine
AB 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-depthinvestigations into their mechanisms of action to reach clinic application in the treatment of cancer. Thiswork 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 waterand exhibit cytotoxic activity in the absence of light irradiation versus several cancer cell lines. Furthermore, thecytotoxic 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 mechanismfor [1a]Cl and [3a]Cl in prostate cancer cells by flow cytometry. These derivatives mainly accumulate in themitochondria as shown by colocalization confocal microscopy experiments. Presumably, [1a]Cl and [3a]Clinduce 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. Bothprocesses seem to be the result of photocatalytic oxidation processes.
PB Elsevier
SN 0162-0134
YR 2022
FD 2022-06
LK http://hdl.handle.net/10259/7444
UL http://hdl.handle.net/10259/7444
LA eng
NO We acknowledge the financial support provided by the Spanish Ministerio de Ciencia, Innovacion ´ y Universidades (RTI2018-100709-BC21, RTI2018-100709-B-C22) and CTQ (QMC)-RED2018-102471-T), Junta de Castilla y Leon ´ (BU087G19), Junta de Comunidades de CastillaLa Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260) and UCLM-FEDER (grants 2019-GRIN-27183 and 2019-GRIN-27209). I. Echevarría wants to acknowledge his fellowship to both the European Social Fund and Consejería de Educacion ´ de la Junta de Castilla y Leon ´ (EDU/1100/2017). E. Zafon wants to acknowledge her predoctoral fellowship to the Generalitat de Catalunya (AGAUR; 2021 FI_B 01036). We are also indebted to Jacinto Delgado, Pilar Castroviejo and Marta Mansilla (PCT of the Universidad de Burgos) for technical support and Jos´e Vicente Cuevas Vicario for advice and support with theoretical calculations and Gabriel García-Herbosa for providing us access to CV equipment.
DS Repositorio Institucional de la Universidad de Burgos
RD 02-may-2024