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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引用次数: 0

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.

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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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