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Background <p>Photothermal therapy (PTT) provides precise and minimally invasive tumor ablation, but its clinical utility is limited by suboptimal photothermal efficiency and inadequate tumor targeting. Single-atom nanozymes (SAzymes) offer high catalytic activity and tunability, yet require further engineering to achieve effective low-dose photothermal-catalytic therapy.</p> Methods <p>We developed an iron single-atom nanozyme modified with arginine-glycine-aspartic acid peptides (Fe-SA@RGD). Structural and chemical features were characterized by advanced microscopy and spectroscopy. Photothermal heating and peroxidase (POD)-like activity were quantified. Cellular uptake, intracellular ROS generation, cytotoxicity, and immunogenic cell death (ICD) biomarkers were evaluated in 4T1 cells. In vivo antitumor efficacy and biosafety were examined in tumor-bearing mice.</p> Results <p>Fe-SA@RGD showed markedly enhanced photothermal performance, reaching 51.1&#xa0;°C at 15&#xa0;μg&#xa0;mL<sup>−1</sup> under 808&#xa0;nm NIR irradiation, which is approximately 10&#xa0;°C higher than unmodified Fe-SA, while preserving robust POD-like activity. At this low dose, Fe-SA@RGD induced significant ROS generation, reduced 4T1 cell viability by 75.0%, and triggered hallmark ICD features. In vivo, Fe-SA@RGD combined with NIR achieved 94.6% tumor growth inhibition with negligible systemic toxicity.</p> Conclusion <p>Fe-SA@RGD integrates enhanced photothermal conversion and intrinsic catalytic activity to achieve low-dose, synergistic photothermal-catalytic tumor ablation and ICD induction. This multifunctional nanoplatform demonstrates potent efficacy, favorable biosafety, and strong potential for precise and immune-active cancer therapy.</p>

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RGD peptide-functionalized iron single-atom nanozyme enables low-dose photothermal and catalytic synergistic therapy with immune activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Ganfa Huang,
  • Dan Li,
  • Jingqi Chen,
  • Yunting Lin,
  • Chunye Chen,
  • Chang Zhao,
  • Weiqing Zhang

摘要

Background

Photothermal therapy (PTT) provides precise and minimally invasive tumor ablation, but its clinical utility is limited by suboptimal photothermal efficiency and inadequate tumor targeting. Single-atom nanozymes (SAzymes) offer high catalytic activity and tunability, yet require further engineering to achieve effective low-dose photothermal-catalytic therapy.

Methods

We developed an iron single-atom nanozyme modified with arginine-glycine-aspartic acid peptides (Fe-SA@RGD). Structural and chemical features were characterized by advanced microscopy and spectroscopy. Photothermal heating and peroxidase (POD)-like activity were quantified. Cellular uptake, intracellular ROS generation, cytotoxicity, and immunogenic cell death (ICD) biomarkers were evaluated in 4T1 cells. In vivo antitumor efficacy and biosafety were examined in tumor-bearing mice.

Results

Fe-SA@RGD showed markedly enhanced photothermal performance, reaching 51.1 °C at 15 μg mL−1 under 808 nm NIR irradiation, which is approximately 10 °C higher than unmodified Fe-SA, while preserving robust POD-like activity. At this low dose, Fe-SA@RGD induced significant ROS generation, reduced 4T1 cell viability by 75.0%, and triggered hallmark ICD features. In vivo, Fe-SA@RGD combined with NIR achieved 94.6% tumor growth inhibition with negligible systemic toxicity.

Conclusion

Fe-SA@RGD integrates enhanced photothermal conversion and intrinsic catalytic activity to achieve low-dose, synergistic photothermal-catalytic tumor ablation and ICD induction. This multifunctional nanoplatform demonstrates potent efficacy, favorable biosafety, and strong potential for precise and immune-active cancer therapy.