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揭示基于层状双氢氧化物的纳米酶减轻缺血再灌注损伤的机制

Unveiling the Mechanism of Alleviating Ischemia Reperfusion Injury a Layered Double Hydroxide-Based Nanozyme.

作者信息

Ma Xiaotong, Zhang Baorui, Ma Na, Liu Chuxuan, Miao Yan, Liang Xin, Guan Shanyue, Li Dawei, Liu Aihua, Zhou Shuyun

机构信息

Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2023 Mar 22;15(11):13869-13878. doi: 10.1021/acsami.2c19570. Epub 2023 Mar 13.

DOI:10.1021/acsami.2c19570
PMID:36914282
Abstract

Oxidative stress after ischemia reperfusion can cause irreversible brain damage. Thus, it is vital to timely consume excessive reactive oxygen species (ROS) and conduct molecular imaging monitoring on the brain injury site. However, previous studies have focused on how to scavenge ROS while ignoring the mechanism of relieving the reperfusion injury. Herein, we reported a layered double hydroxide (LDH)-based nanozyme (denoted as ALDzyme), which was fabricated by the confinement of astaxanthin (AST) with LDH. This ALDzyme can mimic natural enzymes, which include superoxide dismutase (SOD) and catalase (CAT). Furthermore, the SOD-like activity of ALDzyme is 16.3 times higher than that of CeO (a typical ROS scavenger). Based on these enzyme-mimicking properties, this one-of-a-kind ALDzyme offers strong anti-oxidative properties as well as high biocompatibility. Importantly, this unique ALDzyme can establish an efficient magnetic resonance imaging platform, thus guiding the details. As a result, the infarct area can be reduced by 77% after reperfusion therapy, and the neurological impairment score can be lowered from 3-4 to 0-1. Density functional theory computations can reveal more about the mechanism of this ALDzyme's significant ROS consumption. These findings provide a method for unraveling the neuroprotection application process in ischemia reperfusion injury using an LDH-based nanozyme as a remedial nanoplatform.

摘要

缺血再灌注后的氧化应激可导致不可逆的脑损伤。因此,及时清除过量的活性氧(ROS)并对脑损伤部位进行分子成像监测至关重要。然而,以往的研究主要集中在如何清除ROS,而忽略了减轻再灌注损伤的机制。在此,我们报道了一种基于层状双氢氧化物(LDH)的纳米酶(称为ALDzyme),它是通过将虾青素(AST)与LDH结合制备而成。这种ALDzyme可以模拟天然酶,包括超氧化物歧化酶(SOD)和过氧化氢酶(CAT)。此外,ALDzyme的类SOD活性比典型的ROS清除剂CeO高16.3倍。基于这些模拟酶的特性,这种独一无二的ALDzyme具有强大的抗氧化性能以及高生物相容性。重要的是,这种独特的ALDzyme可以建立一个高效的磁共振成像平台,从而指导治疗细节。结果,再灌注治疗后梗死面积可减少77%,神经功能缺损评分可从3 - 4降至0 - 1。密度泛函理论计算可以更深入地揭示这种ALDzyme大量消耗ROS的机制。这些发现为利用基于LDH的纳米酶作为治疗性纳米平台来阐明缺血再灌注损伤中的神经保护应用过程提供了一种方法。

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