Enzyme-triggered supramolecular self-assembly of platinum prodrug with enhanced tumor-selective accumulation and reduced systemic toxicity†
Abstract
We report the generation of a novel self-assembled platinum (Pt) prodrug from a short peptide derivative, which acted as a substrate for the phosphatase-catalyzed dephosphorylation reaction, and a Pt(IV) complex, which could undergo supramolecular self-assembly in the presence of alkaline phosphatase, and perform controlled release of the Pt(II) drug under the reductive conditions of tumor cells. This self-assembled prodrug showed significant antitumor growth effects on a breast cancer xenograft model based on 4T1 cells in vivo, but much lower toxicity towards the kidney, liver, spleen and other major organs than the free cisplatin drug in mice. Such improved antitumor efficacy could be ascribed to the localized and sustained release of the Pt(II) anticancer drug from the supramolecular self-assembly of the Pt(IV) prodrug, which was triggered by phosphatases in tumor sites.
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