School of Chemistry and Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, 541004, People's Republic of China.
Key Laboratory for Analytical Science of Food Safety and Biology (MOE & Fujian Province), Department of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China.
Mikrochim Acta. 2024 Jul 4;191(8):447. doi: 10.1007/s00604-024-06527-6.
An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce HO and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu. The generated Cu and HO triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).
一种由铜掺杂沸石咪唑酯骨架-8（Cu/ZIF-8，简称 CZ）、葡萄糖氧化酶（GOx）、阿霉素（DOX）和透明质酸（HA）组成的智能纳米药物递送系统（Cu/ZIF-8@GOx-DOX@HA，简称 CZGDH）被建立用于肿瘤的靶向药物递送和协同治疗。CZGDH 通过 HA 的靶向作用特异性进入肿瘤细胞，并在肿瘤微环境（TME）中表现出酸性触发的生物降解，随后释放 GOx、DOX 和 Cu。GOx 将肿瘤细胞中的葡萄糖（Glu）氧化生成 HO 和葡萄糖酸，进行饥饿治疗（ST）。DOX 进入肿瘤细胞的细胞核进行化疗（CT）。释放的 Cu 消耗肿瘤细胞中超表达的谷胱甘肽（GSH），产生 Cu。生成的 Cu 和 HO 触发芬顿样反应，产生有毒的羟基自由基（·OH），破坏肿瘤细胞的氧化还原平衡，有效杀死肿瘤细胞，进行化学动力学治疗（CDT）。因此，通过 TME 激活级联反应实现了协同的多模式肿瘤治疗。纳米药物递送系统具有高载药率（48.3wt%），三种模式的协同治疗对肿瘤细胞具有很强的杀伤作用（67.45%）。
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