Platinum catalyst-functionalized cylindrical graft copolymer micelles for dual catalytic and cytotoxic activity†

Catalytic prodrug activation offers a promising approach to cancer therapy, but integrating catalytic and therapeutic functions within a single platform remains challenging. In addition, low-molecular weight metal catalysts suffer from rapid clearance and limited in vivo efficacy. Here, we present a platinum complex-conjugated polymeric micellar system, constructed from amphiphilic poly(acrylic acid)-graft-poly(propylene oxide), which self-assembles into short cylindrical micelles (ca. 50 nm in length) in aqueous solution. The micelles are functionalized with a cisplatin-derived Pt(IV) metal complex, which is released under reductive conditions and converted into catalytically active Pt(II) species capable of deprotecting an N-propargylated 5-fluorouracil prodrug. The catalytic transformation proceeds more efficiently under mildly acidic conditions (pH = 6.0), achieving up to 35% conversion after 96 hours. Cell viability assays using CT26 cancer cells showed a decrease in viability from 60% (Pt-micelle alone) to below 50% when combined with the prodrug, indicating dual catalytic and cytotoxic activity in vitro. These findings provide a proof-of-concept for a dual-functional nanocarrier system capable of localized prodrug activation and therapeutic action, offering a promising strategy for advancing metal-catalyzed cancer therapy.