A modular ROS-responsive platform co-delivered by 10-hydroxycampto-thecin and dexamethasone for cancer treatment

Traditional and single treatment strategies are difficult to achieve good results due to tumor resistance and complex mechanisms. Combination therapy through co-delivery systems is one of the methods to improve the effectiveness of cancer treatment. The polyprodrug platform has inherent advantages such as high drug loading and strong stability. Herein, a new reactive oxygen species (ROS)-responsive micelle composed of poly 10-hydroxycamptothecin (pHCPT) and PEG is reported, which loaded dexamethasone (DEX) as synergistic drugs. The micelles collapse in the complex microenvironment of tumor cells to release DEX. The first released DEX can increase the ROS level of tumor cells, thereby facilitating the cleavage of thioketal bonds to release intact HCPT molecules. Meanwhile, DEX can normalize tumor blood vessels, reduce adverse reactions, and further improve the efficacy of HCPT. This co-delivery system shows an ideal tumor suppressive effect in vivo and in vitro. Designing drugs into a modular multi-drug platform and selecting appropriate synergistic drugs according to the treatment plan provides a convenient strategy for future clinical treatment.