H2O2 Self-Producing Single-Atom Nanozyme Hydrogels as Light-Controlled Oxidative Stress Amplifier for Enhanced Synergistic Therapy by Transforming “Cold” Tumors,Advanced Functional Materials

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H2O2 Self-Producing Single-Atom Nanozyme Hydrogels as Light-Controlled Oxidative Stress Amplifier for Enhanced Synergistic Therapy by Transforming “Cold” Tumors
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2022-01-04 , DOI: 10.1002/adfm.202110268
Daoming Zhu _{1,

2} , Hao Chen ₁ , Chunyu Huang _{1,

2} , Guoxin Li ₁ , Xing Wang ₃ , Wei Jiang ₄ , Kelong Fan _{4,

5}

Affiliation

Single-atom nanozyme (SAzyme) with peroxidase-like activity can alter cellular redox balance and shows promising potential for tumor therapy. However, the “cold” immune microenvironment and limited amount of hydrogen peroxide (H₂O₂) in solid tumors severely restrict its efficacy. Herein, a light-controlled oxidative stress amplifier system is designed by co-encapsulating Pd-C SAzymes and camptothecin in agarose hydrogel, which exhibits enhanced synergistic antitumor activity by self-producing H₂O₂ and transforming “cold” tumors. In this nanozyme hydrogel system, the Pd-C SAzyme converts near-infrared laser into heat, resulting in agarose degradation and consequent camptothecin release. The camptothecin increases H₂O₂ level in tumors by activating nicotinamide adenine dinucleotide phosphate oxidase, improving the catalytic performance of SAzymes with peroxidase-like activity. Moreover, the combination of photothermal therapy, chemotherapy, and nanozyme-based catalytic therapy further facilitates tumor immunogenic death and enhanced antitumor immunity. The results reveal the synergistic antitumor potential of the novel SAzyme/chemotherapeutics-based hydrogel system.

中文翻译：

H2O2 自产单原子纳米酶水凝胶作为光控氧化应激放大器通过转化“冷”肿瘤增强协同治疗

具有类过氧化物酶活性的单原子纳米酶（SAzyme）可以改变细胞的氧化还原平衡，并显示出用于肿瘤治疗的有希望的潜力。然而，实体瘤中“冷”的免疫微环境和有限量的过氧化氢（H ₂ O _{2 ）严重限制了其疗效。}在此，通过将Pd-C SAzymes和喜树碱共包裹在琼脂糖水凝胶中设计了一种光控氧化应激放大器系统，该系统通过自产H ₂ O ₂和转化“冷”肿瘤表现出增强的协同抗肿瘤活性。在这种纳米酶水凝胶系统中，Pd-C SAzyme 将近红外激光转化为热量，导致琼脂糖降解并随之释放喜树碱。喜树碱增加H ₂O ₂水平通过激活烟酰胺腺嘌呤二核苷酸磷酸氧化酶，提高具有类过氧化物酶活性的 SAzymes 的催化性能。此外，光热疗法、化学疗法和基于纳米酶的催化疗法的结合进一步促进了肿瘤免疫原性死亡和增强的抗肿瘤免疫力。结果揭示了新型基于 SAzyme/化疗药物的水凝胶系统的协同抗肿瘤潜力。

更新日期：2022-01-04

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