期刊
ADVANCED HEALTHCARE MATERIALS
卷 7, 期 10, 页码 -出版社
WILEY
DOI: 10.1002/adhm.201701439
关键词
cancer immunotherapy; cytosolic delivery; gold nanoparticles; near-infrared light; vaccine
资金
- Natural Science Foundation of China [81673027, 31670948]
- CAMS Innovation Fund for Medical Sciences [CAMS-I2M-3-026, CAMS-I2M-3-004]
- Tianjin Natural Science Fund for Distinguished Young Scholars [17JCJQJC46400]
- Science and Technology Support Program of Tianjin [14RCGFSY00146]
Cancer vaccines aim to induce a strong major histocompatibility complex class I (MHC-I)-restricted CD8(+) cytotoxic T-cell response, which is an important prerequisite for successful cancer immunotherapy. Herein, a hyaluronic acid (HA) and antigen (ovalbumin, OVA)-decorated gold nanoparticle (AuNPs)-based (HA-OVA-AuNPs) vaccine is developed for photothermally controlled cytosolic antigen delivery using near-infrared (NIR) irradiation and is found to induce antigen-specific CD8(+) T-cell responses. Chemical binding of thiolated HA and OVA to AuNPs facilitates antigen uptake of dendritic cells via receptor-mediated endocytosis. HA-OVA-AuNPs exhibit enhanced NIR absorption and thermal energy translation. Cytosolic antigen delivery is then permitted through the photothermally controlled process of local heat-mediated endo/lysosome disruption by laser irradiation along with reactive oxygen species generation, which helps to augment proteasome activity and downstream MHC I antigen presentation. Consequently, the HA-OVA-AuNPs nanovaccine can effectively evoke a potent anticancer immune response in mice under laser irradiation. This NIR-responsive nanovaccine is promising as a potent vaccination method for improving cancer vaccine efficacy.
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