000132838 001__ 132838
000132838 005__ 20240315113108.0
000132838 0247_ $$2doi$$a10.1039/d3qi02355a
000132838 0248_ $$2sideral$$a137755
000132838 037__ $$aART-2024-137755
000132838 041__ $$aeng
000132838 100__ $$0(orcid)0000-0001-5201-0874$$aRedrado, Marta
000132838 245__ $$aSynthetic ease and exceptional in vivo performance of pyrazole-based cyclometallated iridium complexes
000132838 260__ $$c2024
000132838 5060_ $$aAccess copy available to the general public$$fUnrestricted
000132838 5203_ $$aTwo luminescent cyclometallated IrIII complexes of the type [Ir(C^N)2(N^N)]x (X = 0 (1), and X = +1 (2)) were prepared using methyl 2-phenylquinoline-4-carboxylate as C^N ligands and either a deprotonated or protonated 3-(2-pyridyl)pyrazole as the N^N chelate. The synthesis followed a well-established and straightforward procedure. Photophysical analysis unveiled their remarkable properties, featuring phosphorescent red and orange emissions attributed to 3MLCT and 3LLCT transitions, with high emissive quantum yields in degassed DMSO solutions. Importantly, these complexes exhibited dual functionality as potent chemotherapeutic agents and photosensitisers, with their effectiveness tailored to specific cancer cell lines. Phototherapeutic treatment was particularly effective against lung cancer A549 cells, while a chemotherapeutic approach yielded superior results against breast cancer 4T1-luc2 cells. Both complexes primarily targeted lysosomes, leading to cell death through apoptotic pathways, with IC50 values in the nanomolar range. Importantly, they demonstrated no cytotoxicity against lymphocytes, mimicking the behaviour observed in healthy cells. Encouragingly, 1 and 2 exhibited minimal in vivo toxicity. The most striking finding was the exceptional chemotherapeutic efficacy of complexes 1 and 2 against 4T1-luc2 cells in BALB/c mice. These complexes surpassed the performance of the clinically employed 5-fluorouracil, especially at early tumor stages, significantly retarding 4T1-luc2 proliferation. Further investigations at vascularised and organised tumor stages revealed that complex 1 could reduce tumor size by half compared to untreated mice, which was also confirmed through tumoral weight analysis. While these findings are preliminary, the outstanding performance of these complexes at early tumor stages against breast cancer 4T1-luc2 in vivo, their selective therapeutic feasibility (chemotherapy vs. PDT) tailored to specific cancerous cell lines, and their straightforward synthetic design make them highly attractive candidates for cancer treatment.
000132838 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E07-23R$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136861NB-I00$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-137862NB-I00
000132838 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000132838 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000132838 700__ $$aRomanos, Eduardo
000132838 700__ $$aBenedi, Andrea$$uUniversidad de Zaragoza
000132838 700__ $$aCanudo-Barreras, Guillermo
000132838 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel$$uUniversidad de Zaragoza
000132838 700__ $$0(orcid)0000-0003-0553-0695$$aGimeno, M. Concepción
000132838 700__ $$0(orcid)0000-0002-1218-7218$$aFernández-Moreira, Vanesa$$uUniversidad de Zaragoza
000132838 7102_ $$12010$$2760$$aUniversidad de Zaragoza$$bDpto. Química Inorgánica$$cÁrea Química Inorgánica
000132838 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000132838 773__ $$g11 (2024), 1828-1838$$pInorg. chem. front$$tInorganic Chemistry Frontiers$$x2052-1545
000132838 8564_ $$s3413314$$uhttps://zaguan.unizar.es/record/132838/files/texto_completo.pdf$$yVersión publicada
000132838 8564_ $$s2693421$$uhttps://zaguan.unizar.es/record/132838/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000132838 909CO $$ooai:zaguan.unizar.es:132838$$particulos$$pdriver
000132838 951__ $$a2024-03-15-08:50:55
000132838 980__ $$aARTICLE