Heavy-Atom-Free Dual-Action Dual PACT/PDT action Pt(IV) Prodrug With BODIPY Dimer in Axial Position
Abstract
Photodynamic therapy (PDT) is a clinically approved therapeutic modality with great potential for the treatment of cancers due to its excellent spatiotemporal selectivity and noninvasivenes. A combination of light-controlled chemotherapy (PACT) and PDT in one molecule has the potential to overcome crucial drawbacks of both Pt-based chemotherapy and PDT via a synergetic effect. Herein, we report a Pt(IV)-BODIPY agent for dual light-controlled chemophotodynamic therapy, a Pt(IV) prodrug with a BODIPY orthogonal dimer in the axial position. The orthogonal arrangement of the fluorophores results in a long-lived, "heavy-atom-free" triplet state of the dimeric fluorophore. The high quantum yield of singlet oxygen for the dimer fluorophore and the Pt(IV) prodrug based on it was confirmed, and the formation of the triplet state was demonstrated by flash photolysis. The excellent photosensitive properties of the Pt(IV) prodrug on SK-BR-3 and MCF-7 tumor cells demonstrate photocontrolled toxicity and potential for the development of dual therapy conjugates.
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