Interface cisplatin-crosslinked doxorubicin-loaded triblock copolymer micelles for synergistic cancer therapy

Abstract

Combination chemotherapy is an effective way to improve the therapeutic efficiency in anticancer treatment. Herein, we synthesized a novel amphiphilic triblock copolymer via a two-step ring-opening polymerization (ROP) followed by post-modification. Doxorubicin (DOX) was encapsulated into the copolymeric micelles through hydrophobic interactions, cisplatin (CDDP) was employed to in situ crosslink the interface of DOX-loaded micelles through Pt-carboxyl coordination interaction. The CDDP-mediated crosslinking improved the stability of the micelles and also reduced the release of DOX at physiological pH. After being taken up into the endosome/lysosome, the low environmental pH weakened the Pt-carboxyl coordination interactions, resulting in the destruction of the micelles and the release of CDDP and DOX. Moreover, these micelles loaded with dual drugs enabled a synergistic anticancer effect, showing promise as a potential drug delivery platform for cancer therapy.