Nanomicelle-Based Redox-Responsive Dual-Prodrug for Synergistic Breast Cancer Chemo-Immunotherapy

One of the challenges in antitumor therapy is the precise delivery of the therapeutic agent to cancerous cells. The delivery of chemotherapy agents can benefit from nanoformulation of prodrugs, which integrates the benefits of nanotechnology and prodrugs, including enhanced drug loading, increased drug bioavailability, and targeted accumulation within cancerous cells. In this work, we designed a redox-responsive polymeric dual-prodrug nanocarrier, PL-ss-(C&J), for codelivery of a potent chemotherapeutic camptothecin (CPT) and an immune checkpoint inhibitor JQ1. Further investigations confirmed that the developed nanomedicine was able to respond to the highly reductive environment within tumor cells. Additionally, due to their quick reactions to the intracellular reducing microenvironment, cytotoxic CPT and JQ1 were simultaneously activated and released, exhibiting significant cytotoxicity. This dual-prodrug activation approach also demonstrated high efficiency in inhibiting tumor growth with satisfactory biocompatibility, pharmacokinetics, and safety in vivo. These results indicated that this type of redox-sensitive dual-prodrug codelivery system based on polymeric prodrug nanomicelles would be a promising technology in chemotherapy and immunotherapy.