Xu Xiao-Fan, Chen Jun-Tao, Song Qian, Wang Zhi-Qing, Long Jia-Qin, Mao Guo-Jiang, Li Yongfei, Hu Liufang, Ouyang Juan, Li Chun-Yan
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, Hunan Provincial University Key Laboratory for Environmental and Ecological Health, College of Chemistry, Xiangtan University, Xiangtan, 411105, PR China.
Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, PR China.
Nanoscale. 2025 Jul 3;17(26):15804-15814. doi: 10.1039/d5nr02053k.
Cancer has become a serious threat to human health and the search for a safe and effective treatment method is particularly urgent. Chemodynamic therapy (CDT) is a non-invasive therapeutic method, but CDT still has certain disadvantages such as its limited therapeutic efficacy through overexpression of GSH and single treatment mode. In this paper, ZIF-based nanoparticles called Cu-SK-GOD@ZIF-90 are constructed for improved chemodynamic therapy and dual starvation therapy (ST). The nanoparticles are destroyed by high levels of ATP in cancer cells, releasing Cu, shikonin (SK) and glucose oxidase (GOD). Under the action of Cu and GSH, Cu is generated and catalyzes HO to produce ˙OH for CDT by a Fenton-like reaction. Both the depletion of GSH and the production of HO improve the effect of chemodynamic therapy. Moreover, SK and GOD are used for dual starvation therapy by inhibiting glycolysis and blocking glucose, respectively. experiments have demonstrated that the synergistic combination of CDT and dual ST via treatment with Cu-SK-GOD@ZIF-90 can effectively inhibit the growth of tumors and significantly prolong the survival of mice, and is superior to treatment with Cu@ZIF-90 and Cu-SK@ZIF-90. This synergistic treatment combining CDT and ST offers an effective and safe way to treat cancer.
癌症已成为对人类健康的严重威胁，寻找安全有效的治疗方法尤为迫切。化学动力疗法（CDT）是一种非侵入性治疗方法，但CDT仍存在某些缺点，例如通过谷胱甘肽（GSH）过表达导致其治疗效果有限以及单一治疗模式。本文构建了一种基于沸石咪唑酯骨架结构（ZIF）的纳米颗粒Cu-SK-GOD@ZIF-90，用于改进化学动力疗法和双重饥饿疗法（ST）。癌细胞中高水平的三磷酸腺苷（ATP）会破坏这些纳米颗粒，释放出铜（Cu）、紫草素（SK）和葡萄糖氧化酶（GOD）。在Cu和GSH的作用下，生成Cu并通过类芬顿反应催化过氧化氢（HO）产生羟基自由基（˙OH）用于化学动力疗法。GSH的消耗和HO的产生都提高了化学动力疗法的效果。此外，SK和GOD分别通过抑制糖酵解和阻断葡萄糖用于双重饥饿疗法。实验表明，通过用Cu-SK-GOD@ZIF-90进行治疗，化学动力疗法和双重饥饿疗法的协同组合可有效抑制肿瘤生长并显著延长小鼠生存期，且优于用Cu@ZIF-90和Cu-SK@ZIF-90进行的治疗。这种将化学动力疗法和饥饿疗法相结合的协同治疗为癌症治疗提供了一种有效且安全的方法。
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