Efficacy and mechanism of a biomimetic nanosystem carrying doxorubicin and an IDO inhibitor for treatment of advanced triple-negative breast cancer

Abstract

Abstract As a kind of “cold tumor”, triple-negative breast cancer has a bottleneck in immunotherapy. In this study, mesoporous silica nanoparticles were coated with the chemotherapeutic drug doxorubicin and indoleamine 2, 3-dioxygenase 1 inhibitor 1-MT, and the outer layer was coated with a triple-negative breast cancer cell membrane to construct the tumor dual-targeted delivery system CDIMSN for chemotherapy and immunotherapy, and to investigate the immunogenic death effect of CDIMSN. The system targeted the delivery of tumor therapeutic drugs to the tumor microenvironment. Doxorubicin induced tumor immunogenic death, while 1-MT reversed immunosuppression. In vitro experiments showed that IC50 value of CDIMSN was 0.34µg/ml, significantly lower than that of DIMSN (0.56µg/ml). In vivo findings showed that the tumor size in the CDIMSN group was 2.66-fold and 1.56-fold smaller than that in DOX and DIMSN groups, respectively. CDIMSN group was better than naked DIMSN in stimulating CD8+T cells, CD4+T cells and promoting DCs cell maturation. In addition, blood analysis, biochemical analysis and Hematoxylin staining analysis of mice showed that the bionic nanoparticles had good biological safety.