<br>一种用于增强肿瘤化疗动力学治疗的 pH/GSH 双响应三重协同双金属纳米催化剂,Small

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一种用于增强肿瘤化疗动力学治疗的 pH/GSH 双响应三重协同双金属纳米催化剂
Small ( IF 13.0 ) Pub Date : 2025-01-10 , DOI: 10.1002/smll.202409836
Lu Zhang _{1,

2} , Huan Shen ₂ , Tingting Liu ₃ , Bin Li ₄ , Xi Chen ₂ , Hong Wang ₂ , Chenyang He ₅ , Yang Liu ₁ , Gang Cao ₁ , Shuo Yu ₁

Affiliation

化学动力学疗法（CDT）因其能够通过金属离子介导的催化将肿瘤中过表达的过氧化氢（H₂O₂）转化为剧毒羟基自由基（•OH）而在肿瘤治疗领域引起了广泛关注。然而，CDT 的有效性受到催化剂效率低、肿瘤内 H₂O₂ 水平不足和谷胱甘肽（GSH）过多的阻碍。本研究通过将红细胞膜修饰到负载葡萄糖氧化酶（GOx）的 Fe-Cu 双金属 MOF 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 H₂O₂ 自供应、催化剂自循环和 GSH 自消除的三重增强方式增强了 CDT 的功效。在红细胞膜的促进下在肿瘤组织中积累后，GOx 与葡萄糖发生反应，原位生成 H₂O₂ 和葡萄糖酸。随后，降低的 pH 值触发 CuFeMOF@GOx@Mem 释放 Fe³⁺ 和 Cu²⁺，GSH 立即将其转化为 Fe²⁺ 和 Cu⁺，激活 Fe²⁺ 介导的 Fenton 反应。更重要的是，Cu⁺ 还可以作为 Fe³⁺/Fe²⁺ 转化的促进剂，同时，生成的 Cu²⁺ 可以通过 GSH 进一步还原为 Cu⁺。因此，H₂O₂ 和 Fe²⁺ 的持续积累以及 GSH 的持续消除同时实现，为提高 CDT 的抗肿瘤能力提供了一种独特的方法。

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A pH/GSH Dual-Responsive Triple Synergistic Bimetallic Nanocatalyst for Enhanced Tumor Chemodynamic Therapy

Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (H₂O₂) 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 H₂O₂ 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 H₂O₂ 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 H₂O₂ and gluconic acid in situ. Subsequently, the reduced pH triggers the release of Fe³⁺ and Cu²⁺ from CuFeMOF@GOx@Mem, which is immediately turned into Fe²⁺ and Cu⁺ by GSH, activating the Fe²⁺-mediated Fenton reaction. More importantly, Cu⁺ can also act as an accelerator of Fe³⁺/Fe²⁺ conversion, meanwhile, the generated Cu²⁺ can be further reduced to Cu⁺ by GSH. Consequently, sustained accumulation of H₂O₂ and Fe²⁺ as well as sustained elimination of GSH are achieved simultaneously, providing a unique approach for improving the anti-tumor ability of CDT.

更新日期：2025-01-10

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