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Photoactive platinum(iv) complex conjugated to a cancer-cell-targeting cyclic peptide. | LitMetric
A conjugate of cancer-cell targeting cyclic disulphide nona-peptide c(CRWYDENAC) consisting of nine l-amino acids with the photoactive succinate platinum(iv) complex trans,trans-[Pt(N)(py)(OH)(succinate)] (Pt-cP) has been synthesised and characterised. The conjugate was stable in dark, but released succinate-peptide and Pt(ii) species upon irradiation with visible light, and formed photoproducts with guanine. Conjugate Pt-cP exhibited higher photocytotoxicity than parent complex trans,trans,trans-[Pt(N)(OH)(py)] (FM-190) towards cancer cells, including ovarian A2780, lung A549 and prostate PC3 human cancer cells upon irradiation with blue light (465 nm, 17.28 J cm) with IC values of 2.8-22.4 μM and the highest potency for A549 cells. Even though the dark cellular accumulation of Pt-cP in A2780 cells was lower than that of parent FM-190, Pt from Pt-cP accumulated in cancer cells upon irradiation to a level >3× higher than that from FM-190. In addition, the cellular accumulation of Pt from Pt-cP was enhanced ca. 47× after irradiation.
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