Tumor microenvironment-regulated nanoplatforms for the inhibition of tumor growth and metastasis in chemo-immunotherapy

Chemotherapy is one of the major clinical anticancer therapies. However, its efficiency is limited by many factors, including the complex tumor microenvironment (TME). Herein, manganese-doped mesoporous silica nanoparticles (MM NPs) were constructed and applied to regulate the TME and enhance the efficiency of the combination of chemotherapy and immunotherapy (chemo-immunotherapy). Notably, the combination of MM NPs, doxorubicin hydrochloride, and immune checkpoint inhibitors enhanced the synergistic efficiency of chemo-immunotherapy in a bilateral animal model, which simultaneously inhibited the growth of primary tumors and distant untreated tumors. Moreover, Mn-doping endowed MSNs with six new regulatory functions for the TME by inducing glutathione depletion, ROS generation, oxygenation, cell-killing effect, immune activation, and degradation promotion. These results demonstrated that MM NPs with TME regulatory functions can potentially improve the efficiency of chemo-immunotherapy.