Year: 2024
Type: article
Abstract: Catalysis‐based approaches offer versatile strategies for activating anticancer prodrugs, potentially allowing precise control over drug release and localization within tumor tissues while reducing systemic toxicity. In this study, we explore the role of the phenothiazine dye methylene blue ( MB + ) as a photocatalyst in conjunction with biologically relevant electron donors to facilitate the red‐light conversion of two Pt(IV) complexes, denoted as cis,cis,trans ‐[PtCl 2 (NH 3 ) 2 (O 2 CCH 2 CH 2 COOH) 2 ] ( 1 ) and trans ‐[Pt(O 2 CCH 2 CH 2 COOH) 2 1R,2R‐ (DACH)(ox)] ( 2 ), into cisplatin and oxaliplatin, respectively. Combining spectroscopic techniques (NMR, UV–vis, and flash photolysis) with computational methods, we reveal that the doubly reduced MB + (leucomethylene blue, LMB ) triggers the reductive elimination of axial ligands in the two Pt(IV) precursors, generating the corresponding Pt(II) anticancer drugs. In vitro experiments conducted on the human cervical cancer cell line CaSki, which harbors multiple copies of the integrated HPV‐16 genome, and on nontumoral cells (HaCat) demonstrate that coadministration with Pt(IV) prodrugs improves MB + ’s antiproliferative efficacy in cancer cells, particularly under red light exposure. This enhancement could be attributed to the catalytic production of Pt(II) species within the cellular environment.
Source: ChemCatChem
Institutions: Donostia International Physics Center, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, University of Turin, University of Calabria, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas, University of the Basque Country, Ikerbasque
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Ministerio de Ciencia, Innovación y Universidades, European Commission, Consejo Nacional de Investigaciones Científicas y Técnicas, Eusko Jaurlaritza, Euskal Herriko Unibertsitatea, Università degli Studi di Torino, Università della Calabria, Agencia Estatal de Investigación, NextGenerationEU
Awards: G1066586104, G1175115578, G1200275765, G1338257350, G136813921, G1860105379, G1910954040, G2020244936, G210041235, G2262748287, G2601397997, G2807485940, G300979063, G34346518, G3480869486, G3681454997, G4042783231, G425668148, G5080475149, G5106358108, G5195188938, G5431713967, G544281551, G624877701, G6824885642, G705216429, G7084143925, G7162266856, G7929938928, G884478184, G908812551
OpenAlex ID: W4404251419