All-in-one multifunctional tri-block glycopolymers for targeted delivery of cisplatin and cancer chemotherapy

Cisplatin (CDDP) as a first-line chemotherapy drug has long suffered drawbacks of severe side effects and poor pharmacokinetics. Thus, various nano-carriers of complex architectures and multi-step modifications have been developed to overcome these challenges, but a simple delivery system with integrated multi-functions is still in demand. Herein, we synthesized a new type of glyco-based triple hydrophilic block copolymers for the delivery of CDDP and thereof cancer therapy. The incorporated glucuronic acid part is complexed with CDDP with high entrapment efficiency, while providing pH-responsive release in the acidic tumor microenvironment. The galactose segment is implanted for liver-targeting effect, which can also significantly lower the side effects of CDDP. As a result, the CDDP-loaded nanoparticle PGG2/Pt showed selectively faster endocytosis rates into HepG2 cells in vitro, with the calculated IC 50 value even comparable to that of free CDDP. The in vivo experiments on a HepG2-bearing mouse model, PGG2/Pt showed excellent anti-tumor activity and enhanced drug accumulation on tumor, together with much lowered nephrotoxicity, hepatotoxicity, and splenic toxicity. This work provides a new strategy for CDDP delivery with higher loading efficiency as well as biosafety.