Piezoelectric materials for ultrasound-driven dissociation of Alzheimer's beta-amyloid aggregate structure

Abstract

Piezoelectric materials can evoke electrochemical reactions by transferring charge carriers to reactants upon receiving mechanical stimuli. We report a newly discovered function of piezoelectric bismuth oxychloride (BiOCl) nanosheets for dissociating Alzheimer's beta-amyloid (A beta) aggregates through ultrasound-induced redox reactions. The accumulation of A beta aggregates (e.g., A beta fibrils, plaques) in the central nervous system is a major pathological hallmark of Alzheimer's disease (AD). Thus, clearing A beta aggregates is considered a key for treating AD, but the dissociation of A beta aggregates is challenging due to their extremely robust structure consisting of beta-sheets. BiOCl nanosheets are a biocompatible piezoelectric material with piezocatalytic activity in response to ultrasound. Our analyses using multiple spectroscopic and microscopic tools have revealed that BiOCl nanosheets effectively disassemble A beta fibrils under ultrasound stimulation. Sono-activated BiOCl nanosheets produce piezo-induced oxidative stress, which effectively destabilizes the beta-sheets in A beta fibrils. In vitro evolution has also shown that sono-activated BiOCl nanosheets can effectively alleviate the neuro-toxicity of A beta fibrils. Furthermore, ex vivo evolution demonstrated that amount of A beta plaques in AD mouse's brain slices was drastically reduced by treatment with sono-activated BiOCl nanosheets.