Doxorubicin/CpG self-assembled nanoparticles prodrug and dendritic cells co-laden hydrogel for cancer chemo-assisted immunotherapy

Abstract Conversion of combination cancer therapy from immuno-assisted chemotherapy to chemo-assisted immunotherapy would be a promotion of strategies to highlight the crucial role of immunotherapy. How to improve the efficiency of immunotherapy and reduce the side effect of chemotherapy is the focus of optimization for chemo-assisted immunotherapy. Herein, we designed a doxorubicin/CpG self-assembled nanoparticles prodrug and dendritic cells (DC) co-laden hydrogel system for cancer chemo-assisted immunotherapy. Importantly, DC-based immunotherapy afforded a feasible compensatory treatment for insufficient endogenous DC in vivo by implanting exogenous DC. The pH sensitive nano-prodrug system reduced the side effects of DOX and induced tumor cells to generate tumor antigens. The interaction of tumor antigens and adjuvants with DC could promote the level of antigen presentation, thereby enhancing the immune response. Moreover, the hydrogel scaffold provided a better growth microenvironment to maintain DC viability besides as a carrier for drug and adjuvant. By the merging of doxorubicin-stimulated tumor antigens, DC and adjuvants, they induced a strong CTL killing effect, remarkably increased the infiltration of effector T cells, alleviated the intratumoral immunosuppressive microenvironment and maximized the immune effect for improving the chemo-assisted immunotherapy. In addition, fluorescence imaging tracking of immune cells, chemotherapeutic drugs, and immune adjuvants revealed their in vivo process for efficient therapy, which could afford guidance for the optimization of biomaterials-mediated chemo-assisted immunotherapy.