A biotin guided Pt ^IV amphiphilic prodrug synergized with CDK4/6 inhibition for enhanced tumor targeted therapy

Platinum-based chemotherapy has been the first-line treatment for advanced bladder cancer for decades, but its durability and safety remain important challenges. Targeted delivery and other precision medicine bring hope to fight cancer. In this study, we present a novel targeted therapy utilizing a biotin receptor-targeting lipid Pt^IV prodrug amphiphile, which encapsulates a CDK4/6 inhibitor into BPt^IV@Rib. CDK4/6 inhibitors have the potential to combat breast cancer and enhance sensitivity to cisplatin, thereby improving its therapeutic efficacy. Our findings demonstrate that BPt^IV@Rib also exhibits excellent bladder tumor-targeting capability, resulting in increased accumulation of Pt and ribociclib (Rib) at the tumor site. The combination of Pt^IV and Rib leads to substantial tumor growth suppression while minimizing synergistic toxicity compared to conventional therapies. In conclusion, this combination therapy represents a promising strategy for enhanced targeted treatment of bladder cancer, potentially improving patient outcomes while reducing adverse effects.