经皮微波消融（PMA）是一种用于肝癌的微创热消融方法。然而，PMA的应用受到其产生ROS效率和热效应不足的限制。在本研究中，开发了一种新型微波激活的铜掺杂锆金属有机框架（MOF）（CuZr MOF），用于增强PMA的微波敏化效果。由于离子在大量微孔内的强非弹性碰撞，CuZr MOF具有较强的微波敏感性和高热转化效率，可以显著改善微波热疗（MTT）。此外，由于存在Cu2+离子，CuZr MOF的另一个好处是其类Fenton活性，特别是作为微波动态疗法（MDT）的激发源的微波可以提高类Fenton反应，以最大程度发挥癌症治疗的协同效应。重要的是，CuZr MOF可以通过产生丰富的ROS来抑制热休克蛋白（HSP）的产生，从而增强肿瘤破坏。在机制上，我们发现CuZr MOF+MW治疗通过靶向HMOX1/GPX4轴调节铁死亡介导的肿瘤细胞死亡。总之，本研究开发了一种具有巨大潜力的CuZr MOF微波增敏剂，可通过MTT和MDT协同治疗肝癌。版权所有©2023 Elsevier B.V. 发表。

Percutaneous microwave ablation (PMA) is a thermoablative method used as a minimally invasive treatment for liver cancer. However, the application of PMA is limited by its insufficient ROS generation efficiency and thermal effects. Herein, a new microwave-activated Cu-doped zirconium metal-organic framework (MOF) (CuZr MOF) used for enhanced PMA has a significantly improved microwave sensitizing effect. Owing to the strong inelastic collisions between ions confined in numerous micropores, CuZr MOF has strong microwave sensitivity and high thermal conversion efficiency, which can significantly improve microwave thermal therapy (MTT). Moreover, because of the existence of Cu2+ ions, a further benefit of CuZr MOF is their Fenton-like activity, in particular, microwaves used as an excitation source for microwave dynamic therapy (MDT) can improve the Fenton-like reaction to maximize the synergistic effectiveness of cancer therapy. Importantly, CuZr MOF can inhibit the production of heat shock proteins (HSPs) by producing abundant ROS to enhance tumor destruction. Mechanistically, we found that CuZr MOF + MW treatment modulates ferroptosis-mediated tumor cell death by targeting the HMOX1/GPX4 axis. In summary, this study develops a novel CuZr MOF microwave sensitizer with great potential for synergistic treatment of liver cancer by MTT and MDT.Copyright © 2023. Published by Elsevier B.V.