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仿生设计靶向线粒体的杂交纳米酶作为超氧阴离子清除剂。

Biomimetic Design of Mitochondria-Targeted Hybrid Nanozymes as Superoxide Scavengers.

机构信息

Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.

Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.

出版信息

Adv Mater. 2021 Mar;33(9):e2006570. doi: 10.1002/adma.202006570. Epub 2021 Jan 22.

DOI:10.1002/adma.202006570
PMID:33480459
Abstract

Development of enzyme mimics for the scavenging of excessive mitochondrial superoxide (O ) can serve as an effective strategy in the treatment of many diseases. Here, protein reconstruction technology and nanotechnology is taken advantage of to biomimetically create an artificial hybrid nanozyme. These nanozymes consist of ferritin-heavy-chain-based protein as the enzyme scaffold and a metal nanoparticle core as the enzyme active center. This artificial cascade nanozyme possesses superoxide dismutase- and catalase-like activities and also targets mitochondria by overcoming multiple biological barriers. Using cardiac ischemia-reperfusion animal models, the protective advantages of the hybrid nanozymes are demonstrated in vivo during mitochondrial oxidative injury and in the recovery of heart functionality following infarction via systemic delivery and localized release from adhesive hydrogels (i.e., cardiac patch), respectively. This study illustrates a de novo design strategy in the development of enzyme mimics and provides a promising therapeutic option for alleviating oxidative damage in regenerative medicine.

摘要

利用蛋白质重建技术和纳米技术,仿生地创造出一种人工杂交纳米酶。这种纳米酶由基于铁蛋白重链的蛋白质作为酶支架和金属纳米颗粒核心作为酶活性中心组成。这种人工级联纳米酶具有超氧化物歧化酶和过氧化氢酶类似的活性,并且通过克服多种生物屏障靶向线粒体。通过心脏缺血再灌注动物模型,分别通过系统递送和局部从粘性水凝胶(即心脏贴片)释放,在体内线粒体氧化损伤和梗塞后心脏功能恢复期间,证明了杂交纳米酶的保护优势。该研究说明了酶模拟物开发中的一种全新设计策略,并为缓解再生医学中的氧化损伤提供了一种有前途的治疗选择。

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