Área de Química Inorgánicahttps://hdl.handle.net/10259/113222026-04-19T07:50:38Z2026-04-19T07:50:38ZA Novel Near‐IR Absorbing Ruthenium(II) Complex as Photosensitizer for Photodynamic Therapy and its Cetuximab BioconjugatesMartínez Alonso, MartaGandioso, AlbertThibaudeau, ChloéQin, XueArnoux, PhilippeDemeubayeva, NurikamalGuérineau, VincentFrochot, CélineJung, Alain C.Gaiddon, ChristianGasser, Gilleshttps://hdl.handle.net/10259/113262026-02-05T01:05:50Z2023-08-01T00:00:00ZA Novel Near‐IR Absorbing Ruthenium(II) Complex as Photosensitizer for Photodynamic Therapy and its Cetuximab Bioconjugates
Martínez Alonso, Marta; Gandioso, Albert; Thibaudeau, Chloé; Qin, Xue; Arnoux, Philippe; Demeubayeva, Nurikamal; Guérineau, Vincent; Frochot, Céline; Jung, Alain C.; Gaiddon, Christian; Gasser, Gilles
A novel Ru(II) cyclometalated photosensitizer (PS), Ru-NH2, for photodynamic therapy (PDT) of formula [Ru(appy)(bphen)2]PF6 (where appy=4-amino-2-phenylpyridine and bphen=bathophenanthroline) and its cetuximab (CTX) bioconjugates, Ru-Mal-CTX and Ru-BAA-CTX (where Mal=maleimide and BAA=benzoylacrylic acid) were synthesised and characterised. The photophysical properties of Ru-NH2 revealed absorption maxima around 580 nm with an absorption up to 725 nm. The generation of singlet oxygen (1O2) upon light irradiation was confirmed with a 1O2 quantum yield of 0.19 in acetonitrile. Preliminary in vitro experiments revealed the Ru-NH2 was nontoxic in the dark in CT-26 and SQ20B cell lines but showed outstanding phototoxicity when irradiated, reaching interesting phototoxicity indexes (PI) >370 at 670 nm, and >150 at 740 nm for CT-26 cells and >50 with NIR light in SQ20B cells. The antibody CTX was successfully attached to the complexes in view of the selective delivery of the PS to cancer cells. Up to four ruthenium fragments were anchored to the antibody (Ab), as confirmed by MALDI-TOF mass spectrometry. Nonetheless, the bioconjugates were not as photoactive as the Ru-NH2 complex.
2023-08-01T00:00:00ZPhototoxicity of cyclometallated Ir(III) complexes bearing a thio-bis-benzimidazole ligand, and its monodentate analogue, as potential PDT photosensitisers in cancer cell killingMartínez Alonso, MartaJones, Callum G.Shipp, James D.Chekulaev, DimitriBryant, Helen E.Weinstein, Julia A.https://hdl.handle.net/10259/113252026-02-05T01:05:53Z2024-02-01T00:00:00ZPhototoxicity of cyclometallated Ir(III) complexes bearing a thio-bis-benzimidazole ligand, and its monodentate analogue, as potential PDT photosensitisers in cancer cell killing
Martínez Alonso, Marta; Jones, Callum G.; Shipp, James D.; Chekulaev, Dimitri; Bryant, Helen E.; Weinstein, Julia A.
Two novel cyclometallated iridium(III) complexes have been prepared with one bidentate or two monodentate imidazole-based ligands, 1 and 2, respectively. The complexes showed intense emission with long lifetimes of the excited state. Femtosecond transient absorption experiments established the nature of the lowest excited state as 3IL state. Singlet oxygen generation with good yields (40% for 1 and 82% for 2) was established by detecting 1O2 directly, through its emission at 1270 nm. Photostability studies were also performed to assess the viability of the complexes as photosensitizers (PS) for photodynamic therapy (PDT). Complex 1 was selected as a good candidate to investigate light-activated killing of cells, whilst complex 2 was found to be toxic in the dark and unstable under light. Complex 1 demonstrated high phototoxicity indexes (PI) in the visible region, PI > 250 after irradiation at 405 nm and PI > 150 at 455 nm, in EJ bladder cancer cells.
2024-02-01T00:00:00ZPhotostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible LightJones, Callum G.Martínez Alonso, MartaGagg, HannahKirby, LiamWeinstein, Julia A.Bryant, Helen E.https://hdl.handle.net/10259/113242026-02-05T01:05:52Z2024-09-01T00:00:00ZPhotostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
Jones, Callum G.; Martínez Alonso, Marta; Gagg, Hannah; Kirby, Liam; Weinstein, Julia A.; Bryant, Helen E.
Photodynamic therapy delivers more targeted cell killing than classical chemotherapy. It uses light-absorbing compounds, photosensitizers (PSs), to generate lethal reactive oxygen species (ROS) at sites of localized irradiation. Transition metal complexes are attractive PSs due to their photostability, visible-light absorption, and high ROS yields. Here, we introduce a low-molecular weight, photostable iridium complex, [Ir(thpy)2(benz)]Cl, 1, that localizes to the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs visible light, phosphoresces strongly, generates 1O2 with 43% yield, and undergoes cellular elimination after 24 h. 1 shows low dark toxicity and under remarkably low doses (3 min, 20–30 mJ s–1 cm–2) of 405 or 455 nm light, it causes killing of bladder (EJ), malignant melanoma (A375), and oropharyngeal (OPSCC72) cancer cells, with high phototoxic indices > 100–378. 1 is also an efficient PS in 3D melanoma spheroids, with repeated short-time irradiation causing cumulative killing.
2024-09-01T00:00:00Z