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<p>Protein coronas inevitably cloak nanoparticles <i>in vivo</i>, 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.</p> Graphical Abstract <p></p>

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Nanocorona-engineered gold nanostars orchestrate photothermal augmented immunotherapy and durable cancer vaccination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月3日

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  • Jun Young Park,
  • Su Hyun Lim,
  • Gayeon Kim,
  • Jun-Young Park,
  • Byung-Gil Lee,
  • Sung Jean Park,
  • Youngki Lee,
  • Dongwoo Khang

摘要

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.

Graphical Abstract