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  3. Nanozyme as tumor energy homeostasis disruptor mediated ferroptosis for high-efficiency radiotherapy

Nanozyme as tumor energy homeostasis disruptor mediated ferroptosis for high-efficiency radiotherapy

  • J Colloid Interface Sci. 2025 Jun 15:688:44-58. doi: 10.1016/j.jcis.2025.02.125.
Xingchen Li 1,  Yuxuan Zhang 2,  Annan Liu 1,  Lei Li 1,  Xiaoyu Yang 3,  Yuan Wang 2,  Yuechen Zhao 2,  Andrei V Zvyagin 4,  Tiejun Wang 5,  Quan Lin 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun 130012, China.
  • 2 Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun 130041, China.
  • 3 Department of Orthopedic Surgery, The Second Hospital of Jilin University, Ziqiang Street No. 218, Changchun 130041, China.
  • 4 School of Mathematical and Physical Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia; Research Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • 5 Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun 130041, China. Electronic address: tjwang@jlu.edu.cn.
  • 6 State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun 130012, China. Electronic address: linquan@jlu.edu.cn.
PMID: 39987840 DOI: 10.1016/j.jcis.2025.02.125
Abstract

Radioresistance in tumors, driven by the insufficiency and rapid depletion of Reactive Oxygen Species (ROS), limits the efficacy of radiotherapy (RT). This study introduces an Ir@Au nanozyme that enhances tumor radiosensitivity by disrupting energy homeostasis and inducing Ferroptosis in tumor cells. The Ir@Au nanozyme mimics glucose oxidase to block the tumor's energy supply, continuously produces hydrogen peroxide (H2O2), and lowers the pH to optimize Fenton reactions. Acting as a peroxidase (POD), it generates additional ROS for chemodynamic therapy (CDT), depletes glutathione (GSH), and perturbs the tumor's antioxidant defenses. Upon exposure to ionizing radiation, the nanozyme absorbs photons and emits electrons, interacting with water to amplify ROS production. This ROS accumulation, combined with radiation, enhances DNA damage and lipid peroxidation, reversing radioresistance and promoting Ferroptosis. Additionally, Ir@Au serves as a contrast agent for computed tomography, enabling precise RT through the delineation of tumor boundaries. In summary, the Ir@Au nanozyme effectively disrupts tumor energy homeostasis, initiating ROS-based cascades that inhibit tumor growth. It thus offers a promising strategy for overcoming radioresistance during Cancer therapy.

Keywords

Catalytic cascade reaction; Ferroptosis; Nanozyme; Radiosensitization.

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