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<p>The residual tumors following radiotherapy (RT) often acquire radiation resistance, which not only escalates the risk of damage to surrounding tissues but also compromises the efficacy of subsequent treatments. Various forms of cell death can occur during radiotherapy. Consequently, the newly discovered form of cell death provides an opportunity to enhance the effect of radiotherapy. Here, we developed a biomimetic Cu<sub>2</sub>O@Pt nanozyme-based therapeutic platform for enhancing cuproptosis and regulating tumor microenvironment to enhance RT sensitivity. This platform is composed of Cu<sub>2</sub>O@Pt nanozyme with an outer platelet membrane (named PCP). This engineered PCP nanozyme exhibits a three-tiered radiosensitization functionality. Specifically, it functions as a catalase-mimicking enzyme to catalyzes intracellular H<sub>2</sub>O<sub>2</sub> to supply oxygen, thereby alleviating hypoxic tumor microenvironment (TME). Additionally, it actively targets tumor cells and introduces abundant exogenous Cu ions to induce more dihydrolipoamide S-acetyltransferase oligomerization to down-regulate FDX1 and tricarboxylic acid cycle-related proteins, thereby triggering cuproptosis. Furthermore, it provides Pt elements with high-Z properties to deposit X-ray energy, thus enhancing radiotherapy efficacy from multiple perspectives. Both in vivo and in vitro experiments confirmed the efficacy and biosafety of PCP in combination with RT. This report introduces an innovative strategy for radiosensitization research within the field of nanomedicine, demonstrating significant potential for future applications in precision biomedicine.</p>

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Multifunctional nanozymes enhance radiotherapy sensitivity through cuproptosis induction and hypoxia relief

  • 期刊论文

  • 发表日期：

    2026年4月5日

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  • Yang Zhong,
  • Yaqi Wang,
  • Zhi Chen

摘要

The residual tumors following radiotherapy (RT) often acquire radiation resistance, which not only escalates the risk of damage to surrounding tissues but also compromises the efficacy of subsequent treatments. Various forms of cell death can occur during radiotherapy. Consequently, the newly discovered form of cell death provides an opportunity to enhance the effect of radiotherapy. Here, we developed a biomimetic Cu2O@Pt nanozyme-based therapeutic platform for enhancing cuproptosis and regulating tumor microenvironment to enhance RT sensitivity. This platform is composed of Cu2O@Pt nanozyme with an outer platelet membrane (named PCP). This engineered PCP nanozyme exhibits a three-tiered radiosensitization functionality. Specifically, it functions as a catalase-mimicking enzyme to catalyzes intracellular H2O2 to supply oxygen, thereby alleviating hypoxic tumor microenvironment (TME). Additionally, it actively targets tumor cells and introduces abundant exogenous Cu ions to induce more dihydrolipoamide S-acetyltransferase oligomerization to down-regulate FDX1 and tricarboxylic acid cycle-related proteins, thereby triggering cuproptosis. Furthermore, it provides Pt elements with high-Z properties to deposit X-ray energy, thus enhancing radiotherapy efficacy from multiple perspectives. Both in vivo and in vitro experiments confirmed the efficacy and biosafety of PCP in combination with RT. This report introduces an innovative strategy for radiosensitization research within the field of nanomedicine, demonstrating significant potential for future applications in precision biomedicine.