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.