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

Abstract

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.

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