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Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes. | LitMetric
The Pt(IV) prodrug -[Pt(pyridine)(N)(OH)] () and its coumarin derivative -[Pt(pyridine)(N)(OH)(coumarin-3-carboxylate)] () are promising agents for photoactivated chemotherapy. These complexes are inert in the dark but release Pt(II) species and radicals upon visible light irradiation, resulting in photocytotoxicity toward cancer cells. Here, we have used synchrotron techniques to investigate the in-cell behavior of these prodrugs and visualize, for the first time, changes in cellular morphology and Pt localization upon treatment with and without light irradiation. We show that photoactivation of induces remarkable cellular damage with extreme alterations to multiple cellular components, including formation of vacuoles, while also significantly increasing the cellular accumulation of Pt species compared to dark conditions. X-ray absorption near-edge structure XANES) measurements in cells treated with indicate only partial reduction of the prodrug upon irradiation, highlighting that phototoxicity in cancer cells may involve not only Pt(II) photoproducts but also photoexcited Pt(IV) species.
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