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单原子铂掺杂二氧化铈纳米酶通过心肌细胞靶向摄取和抑制活性氧减轻心肌缺血再灌注损伤。

Single-atom Pt-doped ceria nanozymes mitigate myocardial ischemia reperfusion injury via cardiomyocyte-targeted uptake and suppression of reactive oxygen species.

作者信息

Pu Aoyang, Sim Woo-Sup, Ji Yunseong, Kurian Amal George, Lee Jung-Hwan, Van Anh Bui Thi, Lai Yimin, Hwangbo Hyesoo, Sun Huanhuan, Kim Hae-Won, Park Hun-Jun, Ban Kiwon

机构信息

Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong, China.

Tung Biomedical Sciences Centre, City University of Hong Kong, Kowloon, Hong Kong, China.

出版信息

Bioact Mater. 2025 Jul 20;53:366-385. doi: 10.1016/j.bioactmat.2025.07.019. eCollection 2025 Nov.

DOI:10.1016/j.bioactmat.2025.07.019
PMID:40727484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12302255/
Abstract

The primary treatment for myocardial infarction (MI) is restoring blood flow to the obstructed coronary artery. However, this approach can paradoxically generate reactive oxygen species (ROS), leading to secondary ischemia-reperfusion (IR) injury. Multifunctional nanomaterials present a promising alternative for managing IR injury, offering benefits including cost-effectiveness, robust catalytic stability, and customizable properties that surpass traditional antioxidants. This study explores single-atom Pt-doped ceria nanozymes (Pt@CeNZ) with multi-enzyme mimetic functions facilitated by atomically dispersed Pt. The nanozymes effectively eliminate excess ROS in cardiomyocytes, thereby enhancing cell viability. Notably, Pt@CeNZ demonstrates significantly higher uptake in cardiomyocytes, underscoring its potential as a targeted nanotherapeutic for cardiac tissues. In vivo studies further confirm that Pt@CeNZ treatment substantially reduces infarct size and improves cardiac function following IR injury, without inducing long-term toxicity or inflammation. These findings position Pt@CeNZ as a highly promising heart-targeting nanotherapeutic with potential applications in the acute and long-term treatment of cardiac injuries.

摘要

心肌梗死(MI)的主要治疗方法是恢复受阻冠状动脉的血流。然而,这种方法可能会自相矛盾地产生活性氧(ROS),导致继发性缺血再灌注(IR)损伤。多功能纳米材料为管理IR损伤提供了一种有前景的替代方案,具有成本效益、强大的催化稳定性和超越传统抗氧化剂的可定制特性等优点。本研究探索了具有原子分散的Pt促进的多酶模拟功能的单原子Pt掺杂二氧化铈纳米酶(Pt@CeNZ)。这些纳米酶有效地消除了心肌细胞中过量的ROS,从而提高了细胞活力。值得注意的是,Pt@CeNZ在心肌细胞中的摄取显著更高,突出了其作为心脏组织靶向纳米治疗剂的潜力。体内研究进一步证实,Pt@CeNZ治疗可显著减小IR损伤后的梗死面积并改善心脏功能,且不会引起长期毒性或炎症。这些发现使Pt@CeNZ成为一种极具前景的心脏靶向纳米治疗剂,在心脏损伤的急性和长期治疗中具有潜在应用价值。

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本文引用的文献

1
Oxidative stress modulating nanomaterials and their biochemical roles in nanomedicine.氧化应激调节纳米材料及其在纳米医学中的生化作用。
Nanoscale Horiz. 2024 Sep 23;9(10):1630-1682. doi: 10.1039/d4nh00171k.
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Ferroptosis mechanisms and regulations in cardiovascular diseases in the past, present, and future.铁死亡在心血管疾病中的过去、现在和未来的机制与调控。
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Surface-Engineered Titanium with Nanoceria to Enhance Soft Tissue Integration Via Reactive Oxygen Species Modulation and Nanotopographical Sensing.
表面工程化含纳米氧化铈的钛材通过活性氧物种调节和纳米形貌感知增强软组织整合。
ACS Appl Mater Interfaces. 2024 Mar 20;16(11):13622-13639. doi: 10.1021/acsami.4c02119. Epub 2024 Mar 11.
4
Protective effects of Pt-N-C single-atom nanozymes against myocardial ischemia-reperfusion injury.Pt-N-C 单原子纳米酶对心肌缺血再灌注损伤的保护作用。
Nat Commun. 2024 Feb 23;15(1):1682. doi: 10.1038/s41467-024-45927-3.
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Nanozyme-Engineered Hydrogels for Anti-Inflammation and Skin Regeneration.用于抗炎和皮肤再生的纳米酶工程水凝胶
Nanomicro Lett. 2024 Feb 6;16(1):110. doi: 10.1007/s40820-024-01323-6.
6
Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.缺血再灌注损伤:分子机制与治疗靶点。
Signal Transduct Target Ther. 2024 Jan 8;9(1):12. doi: 10.1038/s41392-023-01688-x.
7
A Cardiac-Targeted Nanozyme Interrupts the Inflammation-Free Radical Cycle in Myocardial Infarction.一种心脏靶向纳米酶可阻断心肌梗死中的无炎症自由基循环。
Adv Mater. 2024 Jan;36(2):e2308477. doi: 10.1002/adma.202308477. Epub 2023 Nov 23.
8
The mechanism of ferroptosis and its related diseases.铁死亡的机制及其相关疾病。
Mol Biomed. 2023 Oct 16;4(1):33. doi: 10.1186/s43556-023-00142-2.
9
Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.靶向氧化应激作为心血管疾病的预防和治疗方法。
J Transl Med. 2023 Aug 2;21(1):519. doi: 10.1186/s12967-023-04361-7.
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Multifunctional dendrimer@nanoceria engineered GelMA hydrogel accelerates bone regeneration through orchestrated cellular responses.多功能树枝状聚合物@纳米氧化铈工程化的明胶甲基丙烯酰基水凝胶通过协调细胞反应加速骨再生。
Mater Today Bio. 2023 May 16;20:100664. doi: 10.1016/j.mtbio.2023.100664. eCollection 2023 Jun.