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.

Automated summary

Manganese-doped mesoporous silica nanoparticles (MM NPs) were used to regulate the tumor microenvironment (TME) and enhance the efficiency of chemotherapy and immunotherapy. The combination of MM NPs, doxorubicin hydrochloride, and immune checkpoint inhibitors showed synergistic efficiency in inhibiting tumor growth in a bilateral animal model. Additionally, Mn-doping endowed MSNs with six new regulatory functions for the TME.