Biomimetic Nanovaccines Potentiating Dendritic Cell Internalization via CXCR4-Mediated Macropinocytosis.
Adv Healthc Mater
; 12(5): e2202064, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36416257
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Melanoma Experimental
/
Vacinas Anticâncer
Limite:
Animals
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Humans
Idioma:
En
Revista:
Adv Healthc Mater
Ano de publicação:
2023
Tipo de documento:
Article