A sulfhydryl blocking reagent BT-4 sensitizes cisplatin-based micelle prodrugs for efficient treatment of breast cancer

•Co-delivery of novel sulfhydryl blocking reagent (BT-4) and CDDP prodrug (C16-Pt(Ⅳ)-PEG) to sensitize CDDP.•BT-4@PtPPNPs with a small particle size (130 nm) was obtained and showed long-term stability in vitro.•The optimized BT-4@PtPPNPs could rapidly target and accumulate within tumors for a long time.•BT-4@PtPPNPs showed notable cytotoxicity due to increased cellular internalization and GSH depletion by BT-4.•BT-4@PtPPNPs inhibited 60.85% tumor growth in 4T1 breast cancer mouse model with a favorable toxicity profile.