Gas Empowered Dual-Cascade Strategy for Augmented Single-Atom Nanotherapies

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Yong Liu, Xiao-Qiong Li, Qiao Yu, Bin Kang, Xueli Zhao, Jing-Juan Xu
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Abstract

Single-atom nanotherapies have received numerous attention in malignant oncotherapy. However, the insufficient enzyme substrate and the upregulation of heat shock proteins during therapeutic interventions are seldom concurrently noticed. Herein, a novel gas empowered dual-cascade synergistic treatment strategy is demonstrated with domino effect, which can sequentially reinforce single-atom nanozyme (SAzyme)-based enzymatic therapeutics and mild photothermal therapy (PTT) (< 45 °C). In the proof-of-concept study, Fe single atom nanozyme (Fe/SAzyme) loaded with hydrogen sulfide (H2S) donor NaHS is developed for HSPs-silencing mediated mild PTT. The generated H2S suppresses the catalase activity to achieve “intracellular H2O2 conservation”, thereby furnishing the enzyme substrate to Fe/SAzyme to produce abundant cytotoxic hydroxyl radicals (·OH) for augmented enzymatic therapeutics. Then, excess ·OH induced mitochondrial dysfunction blocks adenosine triphosphate (ATP) energy supply to realize cellular energy remodeling, which hinders overexpression of HSPs and enhances mild PTT of Fe/SAzyme both in vitro and vivo. Consequently, the gas-triggered dual-cascade strategy achieves domino H2S/·OH/mitochondrial dysfunction synergistic effect, endowing SAzymes with maximum antitumor efficacy via enzymatic therapeutics combined with mild PTT. This dual-cascaded gas/enzymatic/mild PTT synergistic oncotherapy not only exhibits a new pathway for gas-facilitated mild PTT, but also offers a valuable paradigm for the application of “1 + 1 + 1 > 3” multimodal synergistic tumor therapy.

Abstract Image

增强单原子纳米治疗的气体增强双级联策略。
单原子纳米疗法在恶性肿瘤治疗中受到广泛关注。然而,在治疗干预期间,酶底物不足和热休克蛋白上调很少同时被注意到。本研究证明了一种具有多米诺效应的新型气体增强双级联协同治疗策略,该策略可以依次增强基于单原子纳米酶(SAzyme)的酶疗法和轻度光热疗法(PTT)(< 45°C)。在概念验证研究中,开发了负载硫化氢(H2S)供体NaHS的Fe单原子纳米酶(Fe/SAzyme)用于hsps沉默介导的轻度PTT。生成的H2S抑制过氧化氢酶活性,实现“细胞内H2O2保护”,从而为Fe/SAzyme提供酶底物,产生丰富的细胞毒性羟基自由基(·OH),用于增强酶治疗。过量·OH诱导的线粒体功能障碍阻断三磷酸腺苷(adenosine triphosphate, ATP)的能量供应,实现细胞能量重塑,从而抑制HSPs的过表达,增强Fe/SAzyme在体外和体内的轻度PTT。因此,气体触发的双级联策略实现了多米诺骨牌H2S/·OH/线粒体功能障碍协同效应,通过酶治疗联合轻度PTT,赋予SAzymes最大的抗肿瘤功效。这种双级联的气体/酶/轻度PTT协同肿瘤治疗不仅展示了气体促进的轻度PTT的新途径,而且为“1 + 1 + 1 > 3”多模式协同肿瘤治疗的应用提供了有价值的范例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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