Rational Design of Genetically Engineered Mitochondrial-Targeting Nanozymes for Alleviating Myocardial Ischemic-Reperfusion Injury

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2024-12-09 DOI:10.1021/acs.nanolett.4c04462

Xiangyun Zhang, Qiqi Liu, Rongping Zhao, Zhihua Pang, Weiyu Zhang, Tianyi Qi, Mingsheng Zhu, Helong Kang, Meng Qian, Yajuan Wan, Rui Wang, Shufang Wang, Xinglu Huang, Jie Zhuang

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Abstract

The development of mitochondria-targeting nanozymes holds significant promise for treating myocardial ischemia-reperfusion (IR) injury but faces significant biological barriers. To overcome these obstacles, we herein utilized genetically engineered ferritin nanocages (i.e., imFTn) to develop mitochondria-targeting nanozymes consisting of three ferritin subunit assembly modules: an IR-injured cardiomyocyte-targeting module, a lysosome-escaping module, and a mitochondria-targeting module. Using imFTn as a nanozyme platform, we developed nanozymes capable of efficiently catalyzing the l-Arg substrate to produce NO. The imFTn-Ru exhibits NO-generating activities, reduces mitochondrial reactive oxygen species generation, inhibits mitochondrial permeability transition pore opening, and enhances mitochondrial membrane potential. Furthermore, imFTn-Ru provides synergistic effects by specifically targeting myocardial IR-injured tissues, facilitating their accumulation in mitochondria, and protecting mitochondria against myocardial IR-induced injury in both in vitro and in vivo models. This study underscores a rational approach to designing nanozymes for targeting specific subcellular organelles in the treatment of IR injury.

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.