School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China.
Department of Chemistry, Jinzhou Medical University, Jinzhou, 121000, China.
Acta Biomater. 2022 May;144:142-156. doi: 10.1016/j.actbio.2022.03.018. Epub 2022 Mar 14.
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 SIGNIFICANCE: Cerium (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 Zn 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.
基于沸石的纳米材料由于其高孔隙率、生物相容性和生物稳定性，在医学领域有大量的应用。在这项研究中，我们设计了铈（Ce）掺杂的 Linde Type A（LTA）沸石基纳米材料（Ce/Zeo-NMs）作为一种多功能介孔纳米酶，以减轻神经血管单元（NVU）的功能障碍并减轻脑缺血再灌注（I/R）损伤。由于其独特的吸附能力和模拟催化活性，Ce@Zeo-NMs 吸附了过量的锌离子，并表现出对急性 I/R 引起的活性氧（ROS）的清除活性，从而重塑了缺血性大脑中的氧化和锌微环境。体内结果表明，Ce@Zeo-NMs 通过减少梗死面积，通过抑制紧密连接蛋白（TJPs）的降解和抑制小胶质细胞和星形胶质细胞的激活，显著减轻 NVU 对缺血的损伤在大脑中动脉闭塞再灌注（MCAO/R）的大鼠模型中。总之，这些发现表明 Ce@Zeo-NMs 可能成为一种有前途的双重靶向治疗剂，可减轻脑 I/R 损伤。
设计了掺铈的 Linde Type A 沸石基纳米材料（Ce/Zeo-NMs）作为多功能介孔纳米酶，通过减少神经血管单元（NVU）的功能障碍，诱导缺血性中风后的神经保护。Ce@Zeo-NMs 具有吸附过多 Zn 的能力，并表现出模拟酶的活性。结果，Ce@Zeo-NMs 通过改善血脑屏障（BBB）的完整性并抑制小胶质细胞和星形胶质细胞的激活，在大脑中动脉闭塞再灌注（MCAO/R）的大鼠模型中，防止了大脑的缺血并减少了 NVU 的损伤。这些发现表明，Ce@Zeo-NMs 可能成为缺血性中风发作后神经保护和功能恢复的治疗策略。
