一种酶工程无孔铜 (I) 配位聚合物纳米平台，用于基于铜protosis 的协同癌症治疗,Advanced Materials

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一种酶工程无孔铜 (I) 配位聚合物纳米平台，用于基于铜protosis 的协同癌症治疗
Advanced Materials ( IF 27.4 ) Pub Date : 2022-09-02 , DOI: 10.1002/adma.202204733
Yuzhi Xu ₁ , Si-Yang Liu _{2,

3} , Leli Zeng ₁ , Hansu Ma ₁ , Yanfei Zhang ₄ , Huihui Yang ₄ , Yuchen Liu ₁ , Shuo Fang ₁ , Jing Zhao ₁ , Yunsheng Xu ₁ , Charles R Ashby ₅ , Yulong He ₁ , Zong Dai _{2,

3} , Yihang Pan ₁

Affiliation

Cuproptosis 是一种新发现的铜依赖性调节细胞死亡形式，它为探索使用铜基纳米材料诱导 cuprotosis 治疗癌症提供了很好的机会。在这里，葡萄糖氧化酶 (GOx) 工程化的无孔铜 (I) 1,2,4-三唑酸盐 ([Cu(tz)]) 配位聚合物 (CP) 纳米平台，表示为 GOx@[Cu(tz)]，用于饥饿-开发了增强的铜细胞凋亡和光动力协同疗法。重要的是，GOx 的催化活性被屏蔽在无孔支架中，但只有在谷胱甘肽 (GSH) 刺激癌细胞后才能“开启”以有效消耗葡萄糖，从而进行癌症饥饿疗法。葡萄糖和 GSH 的耗尽使癌细胞对 GOx@[Cu(tz)] 介导的铜细胞凋亡敏感，产生脂肪化线粒体蛋白的聚集，铜诱导毒性的目标。细胞内过氧化氢（H₂ O ₂ ) 水平，由于葡萄糖的氧化，激活了 GOx@[Cu(tz)] 的 I 型光动力疗法 (PDT) 功效。体内实验结果表明，GOx@[Cu(tz)] 在携带 5637 个膀胱肿瘤的无胸腺小鼠中产生可忽略不计的全身毒性并抑制肿瘤生长 92.4%。这被认为是首次报道能够诱导铜细胞凋亡和基于铜细胞凋亡的协同治疗膀胱癌的铜质纳米材料，这应该会激发基于铜细胞凋亡的合理设计有效癌症治疗策略的研究。

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An Enzyme-Engineered Nonporous Copper(I) Coordination Polymer Nanoplatform for Cuproptosis-Based Synergistic Cancer Therapy

Cuproptosis, a newly identified form of regulated cell death that is copper-dependent, offers great opportunities for exploring the use of copper-based nanomaterials inducing cuproptosis for cancer treatment. Here, a glucose oxidase (GOx)-engineered nonporous copper(I) 1,2,4-triazolate ([Cu(tz)]) coordination polymer (CP) nanoplatform, denoted as GOx@[Cu(tz)], for starvation-augmented cuproptosis and photodynamic synergistic therapy is developed. Importantly, the catalytic activity of GOx is shielded in the nonporous scaffold but can be “turned on” for efficient glucose depletion only upon glutathione (GSH) stimulation in cancer cells, thereby proceeding cancer starvation therapy. The depletion of glucose and GSH sensitizes cancer cells to the GOx@[Cu(tz)]-mediated cuproptosis, producing aggregation of lipoylated mitochondrial proteins, the target of copper-induced toxicity. The increased intracellular hydrogen peroxide (H₂O₂) levels, due to the oxidation of glucose, activates the type I photodynamic therapy (PDT) efficacy of GOx@[Cu(tz)]. The in vivo experimental results indicate that GOx@[Cu(tz)] produces negligible systemic toxicity and inhibits tumor growth by 92.4% in athymic mice bearing 5637 bladder tumors. This is thought to be the first report of a cupreous nanomaterial capable of inducing cuproptosis and cuproptosis-based synergistic therapy in bladder cancer, which should invigorate studies pursuing rational design of efficacious cancer therapy strategies based on cuproptosis.

更新日期：2022-09-02

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