Zhang Lu, Shen Huan, Liu Tingting, Li Bin, Chen Xi, Wang Hong, He Chenyang, Liu Yang, Cao Gang, Yu Shuo
Department of Thyroid Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710000, China.
Department of Tumor and Immunology in Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710000, China.
Small. 2025 Feb;21(8):e2409836. doi: 10.1002/smll.202409836. Epub 2025 Jan 10.
Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (HO) in tumors into highly toxic hydroxyl radicals (•OH) through metal ion-mediated catalysis. However, the effectiveness of CDT is hindered by low catalyst efficiency, insufficient intra-tumor HO level, and excessive glutathione (GSH). In this study, a pH/GSH dual responsive bimetallic nanocatalytic system (CuFeMOF@GOx@Mem) is developed by modifying red blood cell membranes onto glucose oxidase (GOx)-loaded Fe-Cu bimetallic MOFs, enhancing the efficacy of CDT through a triple-enhanced way by HO self-supply, catalysts self-cycling, and GSH self-elimination. Upon accumulation in tumor tissues facilitated by the red blood cell membrane, the GOx initiates a reaction with glucose to generate HO and gluconic acid in situ. Subsequently, the reduced pH triggers the release of Fe and Cu from CuFeMOF@GOx@Mem, which is immediately turned into Fe and Cu by GSH, activating the Fe-mediated Fenton reaction. More importantly, Cu can also act as an accelerator of Fe/Fe conversion, meanwhile, the generated Cu can be further reduced to Cu by GSH. Consequently, sustained accumulation of HO and Fe as well as sustained elimination of GSH are achieved simultaneously, providing a unique approach for improving the anti-tumor ability of CDT.
化学动力疗法（CDT）因其能够通过金属离子介导的催化作用将肿瘤中过表达的过氧化氢（HO）转化为剧毒的羟基自由基（•OH）而在肿瘤治疗领域备受关注。然而，CDT的有效性受到催化剂效率低、肿瘤内HO水平不足和谷胱甘肽（GSH）过量的阻碍。在本研究中，通过将红细胞膜修饰到负载葡萄糖氧化酶（GOx）的铁铜双金属金属有机框架上，开发了一种pH/GSH双响应双金属纳米催化体系（CuFeMOF@GOx@Mem），通过HO自供应、催化剂自循环和GSH自消除的三重增强方式提高了CDT的疗效。在红细胞膜促进下在肿瘤组织中积累后，GOx引发与葡萄糖的反应，原位生成HO和葡萄糖酸。随后，降低的pH值触发Fe和Cu从CuFeMOF@GOx@Mem中释放出来，它们立即被GSH转化为Fe和Cu，激活Fe介导的芬顿反应。更重要的是，Cu还可以作为Fe/Fe转化的促进剂，同时，生成的Cu可以被GSH进一步还原为Cu。因此，同时实现了HO和Fe的持续积累以及GSH的持续消除，为提高CDT的抗肿瘤能力提供了一种独特的方法。
