Natural Bioactive Compounds Solanesol and Chlorogenic Acid Assembled Nanomicelles for Alzheimer's Disease Therapy

Solanesol (Sol) and chlorogenic acid (CHA) are naturally active compounds. Sol exhibits a significant free radical absorption ability and strong antioxidant activity. CHA, a typical phenolic acid, exhibits excellent anticancer, anti-inflammation, and antibacterial properties. Herein, bifunctional nanomicelles (CI@SPK) were skillfully designed to take advantage of the unique properties of Sol and CHA to treat Alzheimer's disease (AD). Hydrophobic Sol was modified with poly(ethylene glycol) to self-assemble into stable nanomicelles (SP). CHA could be encapsulated into the hydrophobic core of these nanomicelles, which increased its bioavailability greatly. Short peptide K (CKLVFFAED) was incorporated (CI@SPK) to facilitate their crossing the blood-brain barrier. Then, CI@SPK targeted the AD lesion area, and CHA was released in greater quantities with the help of IR780 under irradiation with an 808 nm laser, resulting in synergistically scavenging reactive oxygen species (ROS) with Sol. Consequently, the nanomicelles CI@SPK demonstrated capabilities in scavenging ROS, inhibiting β-amyloid (Aβ) aggregation, and eventually modulating microglia phenotype from M1 to M2 to promote Aβ phagocytosis and clearance. In vivo studies indicated that nanomicelles CI@SPK improved the learning and cognitive impairments of APP/PS1 mice by reducing Aβ plaque and inflammation, signifying the potential value of CI@SPK in clinical application for AD treatment.