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

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 β-amyloid (Aβ) aggregates through ultrasound-induced redox reactions. The accumulation of Aβ aggregates (e.g., Aβ fibrils, plaques) in the central nervous system is a major pathological hallmark of Alzheimer's disease (AD). Thus, clearing Aβ aggregates is considered a key for treating AD, but the dissociation of Aβ aggregates is challenging due to their extremely robust structure consisting of β-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 Aβ fibrils under ultrasound stimulation. Sono-activated BiOCl nanosheets produce piezo-induced oxidative stress, which effectively destabilizes the β-sheets in Aβ fibrils. In vitro evolution has also shown that sono-activated BiOCl nanosheets can effectively alleviate the neuro-toxicity of Aβ fibrils. Furthermore, ex vivo evolution demonstrated that amount of Aβ plaques in AD mouse's brain slices was drastically reduced by treatment with sono-activated BiOCl nanosheets.