Inhibition And Disaggregation Of Amyloid Beta Protein Fibrils Through Conjugated Polymer-Core Thermoresponsive Micelles

Excess aggregation of amyloid beta peptide (A beta) is a fatal cause of Alzheimer's disease (AD), which leads to physiological toxicity. Inhibiting and disaggregating the A beta aggregates is an effective strategy to reduce physiological toxicity in neuronal cells. Herein, conjugated polymer-based thermoresponsive micelles (CPMs) were designed with an efficient thermoresponsive surface and a reactive-oxygen-species (ROS)-generating core. In this work, the CPMs exhibited a strong capability to capture the toxic A beta aggregates at physiological temperature. Under white-light irradiation, ROS was generated in the CPMs, and the toxic A beta aggregates were efficiently disaggregated through the oxidation of ROS, leading to appropriate A beta homeostasis between aggregation and disaggregation and reduced the A beta-induced cytotoxicity. Therefore, the multifunctional micelles of CPMs with both capturing shells and ROS functional cores present a promising strategy to reduce A beta fibrillation-induced cytotoxicity.