Photothermally Controlled MHC Class I Restricted CD8+ T‐Cell Responses Elicited by Hyaluronic Acid Decorated Gold Nanoparticles as a Vaccine for Cancer Immunotherapy

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. Near infrared light (NIR)‐responsive gold nanoparticle‐based nanovaccine enhances the cross‐presentation of vaccines through photothermally controlled endo/lysosome disruption. Subcutaneous administration of this nanovaccine also induces major cytotoxic T lymphocytes (CTL) response accompanied by inhibition of tumor growth. Looking forward, this NIR‐responsive nanovaccine is promising as a potent method of vaccination for improving cancer vaccine efficacy.