Biomimetic Nanovaccines Potentiating Dendritic Cell Internalization via CXCR4‐Mediated Macropinocytosis

• DOI: 10.1002/adhm.202202064
• Publication Date: 2022-11-23T10:57:41Z
• Authors: Chao Yang; Fan Zhang; Fangman Chen; Zhimin Chang; Yuewu Zhao; Dan Shao; Wen Sun; Wen‐fei Dong; Zheng Wang
• Keywords: Pinocytosis; Internalization; Cancer Immunotherapy

Although targeted delivery of nanoparticulate vaccines to dendritic cells (DCs) holds tremendous potential, it still faces insufficient internalization and endosome degradation via the receptor-mediated endocytosis pathway. Inspired by advantages CXC-chemokine receptor type 4 (CXCR4)-mediated macropinocytosis in DCs, a multifunctional vaccine is constructed based on reactive oxygen species (ROS)-responsive core macropinocytosis-inducing peptide-fused cancer membrane shell, allowing direct cytosolic membrane-associated antigen stimulator interferon genes (STING) agonist, cGAMP for highly efficient immunotherapy. The biomimetic nanovaccines show dramatically enhanced cellular uptake DCs CXCR4-mediated macropinocytosis. Such process promotes release response ROS, together promoted DC maturation T cell priming activating STING Consequently, not only result great tumor rejection prophylactic B16-F10 melanoma murine model, but also markedly suppress growth established tumors when combined with anti-PD-1 checkpoint blockade. This study advances design provides promising strategy macropinocytosis-mediated vaccination.