A Biomimic Nanobullet with Ameliorative Inflammatory Microenvironment for Alzheimer's Disease Treatments

Abstract

Aβ oligomers, formed prior to diagnostic marker-amyloid β (Aβ) plaques, can damage neurons and trigger neuroinflammation, which accelerate the neuronal injury in Alzheimer's disease (AD). Herein, the combination of eliminating the Aβ oligomers and alleviating the inflammation is a promising therapeutic strategy for AD. However, the presence of the blood-brain barrier (BBB) and the intrinsic deficiencies of the drugs severely restrict their therapeutic effects. Inspired by the properties of rabies virus, a biomimic nanobullet (PBACR@NRs/SA) targeting neurons has been developed. The biomimic nanobullets possess the BBB penetrating character based on iron oxide nanorods; it can sequentially release rosmarinic acid and small interfering RNA targeting NF-κB triggered by microenvironment, which improve the microenvironment inflammation and realize the cure for AD. Compared with non-biomimic systems, the biomimic nanobullets exhibit a less caveolin-dependent internalization pathway, which reduces ROS production and mitochondrial fission in neurons. Therefore, the biomimic nanobullet is hopeful for the treatment of ADs and provides a promising platform for other brain diseases’ treatments.