Biomimetic Nanovaccines Potentiating Dendritic Cell Internalization via CXCR4-Mediated Macropinocytosis

Adv Healthc Mater. 2023 Feb;12(5):e2202064. doi: 10.1002/adhm.202202064. Epub 2022 Dec 7.

Abstract

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

Keywords: biomimetic; cancer immunotherapy; dendritic cell; macropinocytosis; nanovaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomimetics
  • Cancer Vaccines*
  • Dendritic Cells / metabolism
  • Humans
  • Immunotherapy
  • Melanoma, Experimental*
  • Mice
  • Mice, Inbred C57BL
  • Reactive Oxygen Species / metabolism
  • Receptors, CXCR4 / metabolism

Substances

  • Receptors, CXCR4
  • Reactive Oxygen Species
  • Cancer Vaccines
  • CXCR4 protein, human