O-carboxymethyl chitosan based pH/hypoxia-responsive micelles relieve hypoxia and induce ROS in tumor microenvironment

The hypoxia in tumor microenvironment (TME) can upregulate the HIF-1α and PD-L1 expression and cause immunosuppression of tumor. In this study, a carboxymethyl chitosan-based pH/hypoxia-responsive and γ-Fe2O3/isosorbide dinitrate carrying micelle was designed, and it could catalyze endogenous H2O2 to generate oxygen and relieve hypoxia in TME, so as to relieve the overexpression of HIF-1α and PD-L1 in tumor; meanwhile, it could react with H2O2 to release ROS via Fenton reaction and induce cytotoxicity in tumor. Along with these multiple effects, this carboxymethyl chitosan-based micelles could provide a comprehensive strategy for tumor treatment. [Display omitted] •The CMCS-based micelles can release γ-Fe2O3 and ISDN in hypoxia and low pH.•The micelles can catalyze H2O2 in TME to generate O2 and relieve hypoxia in tumor.•The micelles can downregulate the expression of HIF-1α and PD-L1 in tumor.•The micelles can react with H2O2 to produce ROS and directly kill the tumor cells.•The CMCS-based micelles provided a comprehensive way for tumor treatment.