High-density sub-100-nm peptide-gold nanoparticle complexes improve vaccine presentation by dendritic cells in vitro

高密度亚 100 纳米肽-金纳米粒子复合物可改善树突状细胞体外疫苗呈递

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作者:Adam Yuh Lin, Jessica Lunsford, Adham Sean Bear, Joseph Keith Young, Phillip Eckels, Laureen Luo, Aaron Edward Foster, Rebekah Anna Drezek

Abstract

Nanocarriers have been explored to improve the delivery of tumor antigens to dendritic cells (DCs). Gold nanoparticles are attractive nanocarriers because they are inert, non-toxic, and can be readily endocytosed by DCs. Here, we designed novel gold-based nanovaccines (AuNVs) using a simple self-assembling bottom-up conjugation method to generate high-peptide density delivery and effective immune responses with limited toxicity. AuNVs were synthesized using a self-assembling conjugation method and optimized using DC-to-splenocyte interferon-γ enzyme-linked immunosorbent spot assays. The AuNV design has shown successful peptide conjugation with approximately 90% yield while remaining smaller than 80 nm in diameter. DCs uptake AuNVs with minimal toxicity and are able to process the vaccine peptides on the particles to stimulate cytotoxic T lymphocytes (CTLs). These high-peptide density AuNVs can stimulate CTLs better than free peptides and have great potential as carriers for various vaccine types.

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