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Two-pronged Intracellular Co-delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy

Adv Mater. 2022 Mar 31:e2202168. doi: 10.1002/adma.202202168. Online ahead of print.

ABSTRACT

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co-delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, we developed a lipid-coated iron oxide nanoparticle as nanovaccine (IONP-C/O@LP) that could co-deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome-mediated endocytosis. Such two-pronged cellular uptake pattern enabled IONP-C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibited adjuvant effects by generating intracellular reactive oxygen species, which further promoted DC maturation. IONP-C/O@LP accumulated in the DCs of draining lymph nodes effectively increased the antigen-specific T cells in both tumor and spleen, inhibited tumor growth, and improved animal survival. Moreover, we have demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen-specific immune responses in vivo. This article is protected by copyright. All rights reserved.

PMID:35362203 | DOI:10.1002/adma.202202168

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