Tian Boshi, Tian Ruixue, Liu Shaohua, Wang Yan, Gai Shili, Xie Ying, Yang Dan, He Fei, Yang Piaoping, Lin Jun
Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China.
Key Laboratory of Rare Earth Functional Materials and Applications, Zhoukou Normal University, Zhoukou, 466001, P. R. China.
Adv Mater. 2023 Sep;35(38):e2304262. doi: 10.1002/adma.202304262. Epub 2023 Aug 15.
Piezocatalytic therapy, which generates reactive oxygen species (ROS) under mechanical force, has garnered extensive attention for its use in cancer therapy owing to its deep tissue penetration depth and less O -dependence. However, the piezocatalytic therapeutic efficiency is limited owing to the poor piezoresponse, low separation of electron-hole pairs, and complicated tumor microenvironment (TME). Herein, a biodegradable, porous Mn-doped ZnO (Mn-ZnO) nanocluster with enhanced piezoelectric effect is constructed via doping engineering. Mn-doping not only induces lattice distortion to increase polarization but also creates rich oxygen vacancies (O ) for suppressing the recombination of electron-hole pairs, leading to high-efficiency generation of ROS under ultrasound irradiation. Moreover, Mn-doped ZnO shows TME-responsive multienzyme-mimicking activity and glutathione (GSH) depletion ability owing to the mixed valence of Mn (II/III), further aggravating oxidative stress. Density functional theory calculations show that Mn-doping can improve the piezocatalytic performance and enzyme activity of Mn-ZnO due to the presence of O . Benefiting from the boosting of ROS generation and GSH depletion ability, Mn-ZnO can significantly accelerate the accumulation of lipid peroxide and inactivate glutathione peroxidase 4 (GPX4) to induce ferroptosis. The work may provide new guidance for exploring novel piezoelectric sonosensitizers for tumor therapy.
压电催化疗法可在机械力作用下产生活性氧（ROS），因其具有较深的组织穿透深度且对氧气依赖性较小，在癌症治疗中的应用已引起广泛关注。然而，由于压电响应较差、电子 - 空穴对分离效率低以及肿瘤微环境（TME）复杂，压电催化治疗效率受到限制。在此，通过掺杂工程构建了一种具有增强压电效应的可生物降解多孔锰掺杂氧化锌（Mn-ZnO）纳米簇。锰掺杂不仅会引起晶格畸变以增加极化，还会产生丰富的氧空位（O）来抑制电子 - 空穴对的复合，从而在超声照射下高效产生活性氧。此外，由于锰（II/III）的混合价态，锰掺杂的氧化锌表现出对肿瘤微环境响应的多酶模拟活性和谷胱甘肽（GSH）消耗能力，进一步加剧氧化应激。密度泛函理论计算表明，由于氧空位的存在，锰掺杂可以提高Mn-ZnO的压电催化性能和酶活性。得益于活性氧生成和谷胱甘肽消耗能力的增强，Mn-ZnO可以显著加速脂质过氧化物的积累并使谷胱甘肽过氧化物酶4（GPX4）失活，从而诱导铁死亡。这项工作可能为探索用于肿瘤治疗的新型压电超声敏化剂提供新的指导。
