Abstract
Protein coronas inevitably cloak nanoparticles in vivo, yet their therapeutic potential remains largely untapped. Here we engineer a single-protein nanocorona by adsorbing immunoglobulin G onto PEGylated gold nanostars and reveal a dual-mode antitumor strategy that couples innate and adaptive immunity. Nanocorona formation remodels β-sheets and α-helices secondary structure in IgG and reprograms tumor-associated macrophages toward an M1 phenotype, releasing pro-inflammatory cytokines. Leveraging the photothermal property of the AuS, near-infrared irradiation synergistically induces immunogenic cell death, lowers interstitial fluid pressure, and drives deep infiltration of cytotoxic T lymphocytes while depleting regulatory T cells. In syngeneic CT26 tumor models, the combined nanocorona and photothermal regimen with anti-PD-L1 destroys established tumors significantly and confers complete protection on rechallenge, indicating vaccine-like immune memory. Comprehensive hematology and organ histology show negligible systemic toxicity. These findings position single-protein nanocoronas as stand-alone immunotherapeutics and provide a generalizable blueprint for converting photothermal nanomaterials into multifunctional cancer vaccines.