Protein direct delivery to dendritic cells using nanoparticles based on amphiphilic poly(amino acid) derivatives

被引:142
作者
Akagi, Takami
Wang, Xin
Uto, Tomofumi
Baba, Masanori
Akashi, Mitsuru
机构
[1] Osaka Univ, Grad Sch Engn, Dept Appl Chem, Suita, Osaka 5650871, Japan
[2] Kagoshima Univ, Gard Sch Med & Dent Sci, Ctr Chron Viral dis, Div Antiviral Chemotherapy, Kagoshima 8908544, Japan
[3] Japn Sci & Technol Agcy, Core Res Evolut Sci & technol, Kawaguchi 3320012, Japan
基金
日本科学技术振兴机构;
关键词
nanoparticles; vaccine; protein delivery; dendritic cells; poly(gamma-glutamic acid);
D O I
10.1016/j.biomaterials.2007.04.023
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Induction of an adaptive immune response by vaccination is possible for a broad range of infectious diseases or cancers. Antigen-loaded polymeric nanoparticles have recently been shown to possess significant potential as vaccine delivery systems and adjuvants. Here we demonstrate the use of nanoparticles composed of amphiphilic poly(amino acid) derivatives as vaccine adjuvants. We prepared protein-loaded, biodegradable nanoparticles composed of hydrophobically modified poly(gamma-glutamic acid) (gamma-PGA). gamma-PGA hydrophobic derivatives (gamma-hPGA) formed 200 nm-sized nanoparticles in water. The protein-encapsulated gamma-hPGA nanoparticles were efficiently taken up by immature dendritic cells (iDCs). Interestingly, the nanoparticle uptake by iDCs induced DC maturation. The immunization with human immunodeficiency virus (HIV)-1 gp120-encapsulated nanoparticles strongly induced antigen-specific cellular immunity. These results suggest that antigen-loaded gamma-hPGA nanoparticles provide a novel delivery tool for vaccination against viral infections or tumors. This system has potential application as a universal delivery system for protein-based vaccines capable of inducing cytotoxic T lymphocyte (CTL). (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3427 / 3436
页数:10
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