Simultaneous innate immunity activation and immunosuppression improvement by biodegradable nanoplatform for boosting antitumor chemo-immunotherapy

The suppressive immune microenvironment and the accompanying insufficient immune activation limit the effectiveness of chemotherapy. Here we constructed a nanoplatform ([email protected]2/HA-P-mAb) that can simultaneously activate innate immunity and relieve the immunosuppression to enhance the effect of immune-chemotherapy. The responsive cleavage of peptides (P) in the microenvironment established the basis for the separated and differentiated delivery to tumor cells and regulatory T cells (Tregs). The dropped antibodies (mAb) ran to Tregs to realize the efficacious remission of immunosuppression. Hollow mesoporous manganese dioxide nanoparticles (HMnO2 NPs) coated with hyaluronic acid (HA) could achieve tumor targeting and rapid glutathione-responsive degradation in tumor cells. Interestingly, benefiting from the collapse of the HMnO2 NPs, the large supply of curcumin analogue (CA-1) not only induced the apoptosis of cancer cells, but also improved their immunogenicity. Meanwhile, the released manganese could increase the production of inflammatory factors such as type I interferon by activating the stimulator of interferon genes pathway. The pro-inflammatory dominance and enhanced tumor immunogenicity resulting from the factors above, which further led to the maturation of dendritic cells (DCs) and the recruitment of cytotoxic T cells. [email protected]2/HA-P-mAb NPs completed the remodeling of the tumor immune microenvironment and had satisfactory anti-tumor effect on tumor-bearing mice. Therefore, this novel platform may offer therapeutic potential for cancer chemo-immunotherapy.