Self-assembled quercetin-conjugated nanoparticles for potential treatment of Alzheimer’s disease

Abstract Oxidative stress and inflammation are important pathologic factors for the progression of Alzheimer’s disease (AD). The alleviation of oxidative stress and inflammation is regarded as an effective strategy for the treatment of AD. Herein, benefiting from the strong anti-oxidative and anti-inflammatory capability of quercetin (QC), we fabricate QC-loaded nanoparticles (QC NPs) for potential treatment of AD. QC is conjugated to phenylboronic acid modified hyaluronic acid by the formation of phenylboronate ester bonds, which is further assembled into QC NPs owing to the amphiphilic property. QC can be efficiently released from QC NPs under the stimulation of acidic pH or H2O2, due to the cleavage of dynamic phenylboronate ester bonds. The released QC from QC NPs significantly reduces intracellular ROS level and down-regulates pro-inflammatory cytokines (TNF-α and IL-6) in model AD cells, thereby alleviating Aβ25-35 induced cytotoxicity. This research brings up an effective strategy for potential treatment of AD.