Tumor-Antigen Activated Dendritic Cell Membrane-Coated Biomimetic Nanoparticles with Orchestrating Immune Responses Promote Therapeutic Efficacy against Glioma.

Abstract

Immunotherapy has had a profound positive effect on certain types of cancer but has not improved the outcomes of glioma because of the blood-brain barrier (BBB) and immunosuppressive tumor microenvironment. In this study, we developed an activated mature dendritic cell membrane (aDCM)-coated nanoplatform, rapamycin (RAPA)-loaded poly(lactic-<i>co</i>-glycolic acid) (PLGA), named aDCM@PLGA/RAPA, which is a simple, efficient, and individualized strategy to cross the BBB and improve the immune microenvironment precisely. <i>In vitro</i> cells uptake and the transwell BBB model revealed that the aDCM@PLGA/RAPA can enhance homotypic-targeting and BBB-crossing efficiently. According to the <i>in vitro</i> and <i>in vivo</i> immune response efficacy of aDCM@PLGA/RAPA, the immature dendritic cells (DCs) could be stimulated into the matured status, which leads to further activation of immune cells, such as tumor-infiltrating T cells and natural killer cells, and can induce the subsequent immune responses through direct and indirect way. The aDCM@PLGA/RAPA treatment can not only inhibit glioma growth significantly but also has favorable potential ability to induce glial differentiation in the orthotopic glioma. Moreover, the aDCM@PLGA could induce a robust CD8⁺ effector and therefore suppress orthotopic glioma growth in a prophylactic setup, which indicates certain tumor immunity. Overall, our work provides an effective antiglioma drug delivery system which has great potential for tumor combination immunotherapy.