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  • Title: Photoactive monofunctional platinum(II) anticancer complexes of multidentate phenanthridine-containing ligands: photocytotoxicity and evidence for interaction with DNA.
    Author: Lozada IB, Gussakovsky D, Jayawardhana AMDS, McKenna SA, Zheng YR, Herbert DE.
    Journal: Photochem Photobiol Sci; 2023 Nov; 22(11):2587-2597. PubMed ID: 37725299.
    Abstract:
    Pt(II) complexes supported by chelating, multidentate ligands containing π-extended, planar phenanthridine (benzo[c]quinoline) donors (RLPtCl) exhibit a promising in vitro therapeutic index compared with phenanthriplatin, a leading preclinical anticancer complex containing a monodentate phenanthridine ligand. Here, we report evidence for non-specific interactions of CF3LPtCl with DNA through intercalation-mediated turn-on luminescence in O2-saturated aqueous buffer. Brief irradiation with visible light (490 nm) was also found to drastically increase the activity of CF3LPtCl, with photocytotoxicity increased up to 87% against a variety of human cancer cell lines. Mechanistic studies highlight significantly improved cellular uptake of CF3LPtCl compared with cisplatin, with localization in the nucleus and mitochondria triggering effective apoptosis. Photosensitization experiments with 1,3-diphenylisobenzofuran demonstrate that CF3LPtCl efficiently mediates the generation of singlet dioxygen (1O2), highlighting the potential of RLPtCl in photodynamic therapy.
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