Redox-responsive chondroitin sulfate-based micelle system for enhanced chemotherapy and inflammation suppression to synergistically antitumor therapy

According to the close association between cancer and inflammation demonstrated in clinical data, the strategy of synergistic anti-tumor and anti-inflammatory therapy shows promising potential. However, challenges remain in the synthesis and development of co-delivery systems for synergistic therapy. Herein, an amphiphilic chondroitin sulfate-rosmarinic acid polymeric prodrug was synthesized, and then combined with DSPE-PEG to encapsulate doxorubicin, forming a redox-responsive nanomicelle (PRSC/DOX) delivery system. PRSC/DOX exhibited a particle size of 188.6 nm and remained stable in PBS for at least 7 days. PRSC/DOX was internalized into tumor cells via CD44 receptor-mediated endocytosis, and degraded by intracellular glutathione to release the drugs. The released doxorubicin killed tumor cells through chemotherapy, and rosmarinic acid inhibited tumor cell growth by suppressing inflammation levels in the tumor microenvironment. In vivo experiments showed a statistically significant decrease in the inflammation levels in mice, along with a considerable reduction in tumor volume. Consequently, the PRSC/DOX significantly enhanced antitumor efficacy through a synergistic therapy of chemotherapy and inflammation suppression.