Wireless Uncaging of Boronates in Living Cells via Piezocatalytically Generated H₂O₂

Piezoelectric materials offer wireless bond cleavage in remote areas using ultrasound or other mechanical pressure. Although this approach has enormous therapeutic application potential, the appropriate design of such materials is limited and yet to be explored. In this study, we demonstrate the use of BaTiO₃ nanoparticles for piezocatalytic bond cleavage and the controlled release of organic boronates within live cells, facilitated by medical-grade ultrasound. We demonstrated that piezocatalytically generated hydrogen peroxide (H₂O₂) can facilitate bond cleavage without inducing cytotoxicity. However, this process requires optimization of nanoparticle shape, with nanospheres proving to be more suitable compared to nanorods or nanowires. We have demonstrated piezocatalytic uncaging of various biorelevant organic boronates via deboronative hydroxylation outside/inside living cells, and extended this approach to 3D tumor spheroid models. The proposed approach offers a promising pathway for the ultrasonic activation of boronate-based drugs in remote areas of the body, enabling enhanced therapeutic performance.