Reductants supplement boost the antitumor efficacy of nanomedicine

The elevated redox state has become a distinctive characteristic in the tumor environment for designing novel nanomedicines. However, the excessive oxidation stress brought out several plights, such as insufficient reduction-responsive drug release, dense extracellular matrix, and immunosuppressive tumor microenvironment. Here, we explored a potential strategy of replenishing exogenous reductants to boost the efficacy of nanomedicines. Disulfide bond-bridged cabazitaxel prodrug nanoassemblies were developed with high drug loading and reduction responsivity. As relying on endogenous reductants only was not sufficient enough to trigger the activation of prodrug, exogenous reductants were further supplemented to accelerate the activation efficiency. In addition, we found exogenous reductants would increase the tumor penetration of prodrug nanoassemblies, reverse the immunosuppressive system caused by high oxidation stress, and mediate a remarkable antitumor efficacy combined with Anti-PD1. This work elucidated the functions of reductants in cancer treatment, and highlighted their prominent role in combination with nanomedicines.