An Approach to Apply BDNF Targeting Fe3O4-Based Nanoparticles as Multifunctional Anti-Alzheimer Agents.

To search for novel anti-Alzheimer agents, multifunctional Fe3O4-based nanoparticles (FSSIO) is designed and prepared which contain ferulic acid (FA) and Simvastatin linked to the surface of Fe3O4 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.