An Enzyme-Engineered Coppery Nanozyme for High-Efficiency Mild Photothermal/Chemodynamic/Starvation Therapy Through Self-Reinforcing Cancer Energy Metabolism Regulation,Advanced Functional Materials

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An Enzyme-Engineered Coppery Nanozyme for High-Efficiency Mild Photothermal/Chemodynamic/Starvation Therapy Through Self-Reinforcing Cancer Energy Metabolism Regulation
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-02-05 , DOI: 10.1002/adfm.202313853
Yulong Bian _{1,

2} , Bin Liu _{1,

3} , Binbin Ding ₁ , Meng Yuan _{1,

2} , Chunzheng Yang _{1,

2} , Kai Li ₁ , Mengyu Chang ₄ , Abdulaziz A. Al Kheraif ₅ , Ping'an Ma _{1,

2} , Jun Lin _{1,

2}

Affiliation

Photothermal therapy (PTT) has a great prospect in further improving tumor therapeutic outcomes, whereas its efficiency is restrained by low light penetration, excessive heat damage to normal tissues, up-regulated heat shock proteins (HSPs), and limited effect of single treatment. Herein, an enzyme-engineered coppery nanozyme based on dendritic mesoporous coppery carbon nanosphere as the cornerstone to load with glucose oxidase (GOx) followed by modification with hyaluronic acid is constructed. Density functional theory calculations indicate that the obtained coppery nanozyme exhibits peroxidase and glutathione oxidase mimicking activities to improve hydroxyl radicals (•OH) production. Furthermore, both the generation of •OH production and GOx-induced energy supply blockade can reduce HSPs expression to enhance the mild PTT (η = 34.9 %) of coppery nanozyme upon the irradiation of 1064 nm laser, and in turn, accelerate the catalytic processes of coppery nanozyme for more generation of •OH. Last but not least, the introduction of copper can induce lipoylated protein dihydrolipoamide S-acetyltransferase aggregation to cause cellular cuproptosis. Due to the synergy of multiple therapies, the tumor inhibition rate can reach 93.4%. Overall, this work provides an effective strategy for potential tumor treatment on the basis of synergistic therapies.

中文翻译：

酶工程铜纳米酶通过自我强化癌症能量代谢调节实现高效温和光热/化学动力学/饥饿疗法

光热疗法（PTT）在进一步改善肿瘤治疗效果方面具有广阔的前景，但其效率受到光穿透性低、对正常组织过度热损伤、热休克蛋白（HSP）上调以及单次治疗效果有限等因素的限制。本文构建了一种酶工程铜纳米酶，以树枝状介孔铜碳纳米球为基石，负载葡萄糖氧化酶（GOx），然后用透明质酸进行修饰。密度泛函理论计算表明，所获得的铜纳米酶表现出过氧化物酶和谷胱甘肽氧化酶模拟活性，可改善羟基自由基（·OH）的产生。此外，在 1064 nm 激光照射下，·OH 的产生和 GOx 诱导的能量供应阻断都可以减少 HSP 的表达，从而增强铜纳米酶的温和 PTT (η = 34.9 %)，从而加速催化过程铜纳米酶可产生更多的·OH。最后但并非最不重要的一点是，铜的引入可以诱导硫辛酰化蛋白二氢硫辛酰胺S-乙酰转移酶聚集，从而引起细胞铜凋亡。由于多种疗法的协同作用，肿瘤抑制率可达93.4%。总的来说，这项工作为基于协同疗法的潜在肿瘤治疗提供了有效的策略。

更新日期：2024-02-05

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