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.

Engineering precision nanoparticles for drug delivery

“…Antigen-presenting cells (APCs) that take up these NP systems present the antigen cargo to T cells to prime and activate them. NPs used in these systems can be polymeric (PLGA) 226 , lipid-based (liposomes, LNPs) 227 , 228 , inorganic (gold, silica) 229 , 230 or biologically derived (cell-membrane vesicles) 231 , 232 . NP-based cancer vaccines are currently being used in clinical trials 233 .…”

Polysaccharide-based nanomedicines for cancer immunotherapy: A review

“…Besides HA (ase)-PEI nanosystems, nanosystems made from HA, OVA and gold (Au) particles have also been applied for immunotherapy [ 51 ] ( Fig. 5 ).…”

Electromagnetic Nanomedicines for Combinational Cancer Immunotherapy

“…OVA-ICG-labeled DCs were observed in the popliteal lymph node of living mice after injection (Figure 5f), verifying the migration of DCs from the initial injection site to the draining lymph node,w hich was essential for activation of immune response.Inanother study,agold NP-based nanovaccine was developed for photothermally induced immunotherapy. [44] Thiolated hyaluronic acid (HA) and OVAw ere covalently decorated onto gold NPs.T he surface modification of HA facilitated uptake of the nanovaccine by DCs via endocyctosis mediated by the interaction between HA and the cluster of differentiation 44 (CD44). Under NIR laser irradiation at 808 nm, gold NPs in endo/lysosomes produced heat via PTT effect to disrupt the endo/lysosomal membrane,leading to the release of OVAi nto the cytosol.…”