智能纳米药物递送系统（Cu/ZIF-8@GOx-DOX@HA，以下简称 CZGDH）由 Cu 掺杂沸石咪唑酯骨架 8（Cu/ZIF-8，以下简称 CZ）、葡萄糖氧化酶 (GOx)、阿霉素 ( DOX）和透明质酸（HA）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，并表现出酸度触发的生物降解作用，随后在肿瘤微环境 (TME) 中释放 GOx、DOX 和 Cu2。 GOx 氧化肿瘤细胞中的葡萄糖 (Glu)，产生 H2O2 和葡萄糖酸，用于饥饿疗法 (ST)。 DOX进入肿瘤内细胞核进行化疗（CT）。释放的 Cu2 消耗肿瘤细胞中过度表达的谷胱甘肽（GSH）以产生 Cu2+。生成的Cu和H2O2引发类芬顿反应，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，用于化学动力学治疗（CDT）。因此，通过TME激活的级联反应实现了协同多模式肿瘤治疗。该纳米药物递送系统具有较高的载药率（48.3wt%），三模式协同治疗对肿瘤细胞具有很强的杀伤作用（67.45%）。© 2024。作者，获得Springer独家许可-Verlag GmbH Austria，施普林格·自然集团的一部分。

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 Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 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%).© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.