Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research and Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
Nanjing University of Chinese Medicine, Nanjing, 210046, China.
Small. 2024 Nov;20(48):e2403625. doi: 10.1002/smll.202403625. Epub 2024 Sep 6.
To search for novel anti-Alzheimer agents, multifunctional FeO-based nanoparticles (FSSIO) is designed and prepared which contain ferulic acid (FA) and Simvastatin linked to the surface of FeO particles. In vitro tests confirmed that FSSIO possessed favorable biocompatibility and a pronounced ability to penetrate blood brain barrier. The FA moiety endowed the particles with remarkable antioxidant and anti-inflammatory properties, and effectively protected neuron cells from the toxicity induced by Aβ. Moreover, the Simvastatin pharmacophore assists the particles up-regulate the expression level of BDNF and significantly promotes the expression levels of p-TrkB, p-ERK, p-PI3K and Akt, which consequently leads to the neurite outgrowth via regulating PI3K/ATK and TrkB-mediated signaling pathway. More importantly, in the Morris water maze test, FSSIO shows excellent activity to enhance the learning and memory retention of AD model rats.
为了寻找新型抗阿尔茨海默病药物，设计并制备了具有多功能的基于 FeO 的纳米粒子（FSSIO），该纳米粒子含有与 FeO 颗粒表面相连的阿魏酸（FA）和辛伐他汀。体外试验证实，FSSIO 具有良好的生物相容性和显著的穿透血脑屏障的能力。FA 部分使颗粒具有显著的抗氧化和抗炎特性，可有效保护神经元细胞免受 Aβ诱导的毒性。此外，辛伐他汀药效团有助于颗粒上调 BDNF 的表达水平，并显著促进 p-TrkB、p-ERK、p-PI3K 和 Akt 的表达水平，从而通过调节 PI3K/ATK 和 TrkB 介导的信号通路促进神经突生长。更重要的是，在 Morris 水迷宫测试中，FSSIO 表现出优异的活性，可增强 AD 模型大鼠的学习和记忆保留能力。
