Ovalbumin Functionalized Au-Pd Nanodumbbells Enable Photothermal-Immunotherapy With OVA-Associated Immune Activation

Melanoma remains highly lethal due to rapid progression and limited response to conventional therapies. Photothermal therapy (PTT) offers precise tumor ablation, yet its efficacy is restricted by shallow light penetration and weak immunogenicity. Here, we develop a multifunctional immuno-photothermal nanoplatform based on bimetallic Au-Pd nanodumbbells coated with a genipin crosslinked ovalbumin (OVA) antigenic shell (AuPd-G-OVA NDs). The bilateral Pd coating enhances NIR-II (1064 nm) absorption and photothermal conversion, enabling effective NIR-II heating. Genipin crosslinking provides stable antigen loading and promotes dendritic cell activation. Upon irradiation, AuPd-G-OVA NDs induce potent photothermal ablation and promote reactive oxygen species (ROS)-mediated oxidative stress with ICD-associated immunogenic damage, facilitating enhanced antigen presentation and OVA-associated T-cell responses. In vivo, this platform significantly suppresses B16-OVA melanoma growth and elicits durable systemic antitumor immunity. These findings demonstrate a synergistic strategy integrating PTT with OVA-associated immunotherapy, offering a promising approach for advanced melanoma treatment.