Synergistical chemotherapy and cancer immunotherapy using dual drug-delivering and immunopotentiating mesoporous silica

Abstract

Combination of chemotherapy and cancer immunotherapy is a promising approach for cancer treatment. Mesoporous silica has a dual function of chemotherapy drug delivery carrier and immunopotentiator. Herein, thin shell hollow mesoporous silica (tHMS) nanospheres with shell thickness about 20nm and mesopores about 2–4nm on the shells were used for cancer immunochemotherapy. The tHMS nanospheres are good carriers for doxorubicin (DOX), owing to their high loading efficacy, pH-dependent release behavior and significantly stronger cytotoxic efficacy than free DOX against E.G7-OVA cells. Intratumoral injection of DOX-loaded tHMS nanospheres in combination with intraperitoneal administration of anti-CTLA4 antibody not only inhibits treated tumor growth, but also rejects untreated distant tumor growth. The present immunochemotherapy using tHMS nanospheres promotes tumor cell apoptosis, increases macrophages, dendritic cells and neutrophils accumulation in dying tumor tissues, decreases CTLA4+ expression and enhances IFNγ+ expression in T cells of mice. Our findings suggest that the strategy to use chemotherapy drug-delivering and immunopotentiating functions of tHMS nanospheres, in combination with immune checkpoint blockade therapy, is an effective way to generate synergistical chemotherapy and immunotherapy in cancer treatment.