A biomimetic zeolite-based nanoenzyme contributes to neuroprotection in the neurovascular unit after ischaemic stroke via efficient removal of zinc and ROS
A biomimetic zeolite-based nanoenzyme contributes to neuroprotection in the neurovascular unit after ischaemic stroke via efficient removal of zinc and ROS
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DOI：
10.1016/j.actbio.2022.03.018
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发表时间：
2022-05-05
影响因子：
9.7
通讯作者：
Zhao, Liang
中科院分区：
文献类型：
--
作者：
Huang, Zhixuan;Qian, Kun;Zhao, Liang
沸石基纳米材料由于其高孔隙率、生物相容性和生物稳定性在医学领域有着广泛的应用。在这项研究中，我们设计了铈（Ce）掺杂的Linde A型（LTA）沸石基纳米材料（Ce/Zeo-NM）作为一种多功能介孔纳米酶，以减少神经血管单位（NVU）功能障碍，减轻脑缺血再灌注（I/R）损伤。由于其独特的吸附能力和模拟催化活性，Ce@Zeo-NMs吸附过量的锌离子，并表现出清除活性对活性氧（ROS）诱导的急性I/R，从而重塑氧化和锌在缺血脑微环境。体内结果表明，Ce@ Zeo-NM通过减少梗塞面积，通过抑制紧密连接蛋白（TJPs）的降解和抑制大脑中动脉闭塞-再灌注（MCAO/R）大鼠模型中小胶质细胞和星形胶质细胞的活化来保护血脑屏障（BBB）免于破裂，从而显著降低对NVU的缺血性损伤。研究结果表明，Ce@ Zeo-NM有望成为一种双靶向治疗剂，用于减轻脑缺血再灌注损伤。重要性声明Ce/Zeo-NM是一种多功能介孔纳米酶，可通过减少神经血管单位（NVU）功能障碍来诱导缺血性脑卒中后的神经保护作用。Ce@ Zeo-NM具有吸附过量Zn 2+的能力，并显示出模拟酶活性。结果表明，Ce@ Zeo-NM通过改善血脑屏障（BBB）的完整性和抑制小胶质细胞和星形胶质细胞的活化，对大脑中动脉闭塞再灌注（MCAO/R）大鼠模型的脑缺血和NVU损伤具有保护作用。这些发现表明Ce@ Zeo-NM可作为缺血性卒中发作后神经保护和功能恢复的治疗策略。(C)2022 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Zeolite-based nanomaterials have a large number of applications in the field of medicine due to their high porosity, biocompatibility and biological stability. In this study, we designed cerium (Ce)-doped Linde Type A (LTA) zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme to reduce dysfunction of the neurovascular unit (NVU) and attenuate cerebral ischaemia-reperfusion (I/R) injury. Owing to its unique adsorption capacity and mimetic catalytic activities, Ce@Zeo-NMs adsorbed excess zinc ions and exhibited scavenging activity against reactive oxygen species (ROS) induced by acute I/R, thus reshaping the oxidative and zinc microenvironment in the ischaemic brain. In vivo results demonstrated that Ce@Zeo-NMs significantly reduced ischaemic damage to the NVU by decreasing the infarct area, protecting against breakdown of the blood-brain barrier (BBB) via inhibiting the degradation of tight junction proteins (TJPs) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Taken together, these findings indicated that Ce@Zeo-NMs may serve as a promising dual-targeting therapeutic agent for alleviating cerebral I/R injury.Statement of SignificanceCerium (Ce)-doped Linde Type A zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme were designed for inducing neuroprotection after ischaemic stroke by reducing dysfunction of the neurovascular unit (NVU). Ce@Zeo-NMs had the ability to adsorb excessive Zn2+ and showed mimetic enzymatic activities. As a result, Ce@Zeo-NMs protected against cerebral ischaemia and reduced the damage of NVU by improving the integrity of blood brain barrier (BBB) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). These findings indicated that Ce@Zeo-NMs may serve as a therapeutic strategy for neuroprotection and functional recovery upon ischaemic stroke onset. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.