Remote Molecule Activation in Living Mice Triggered by Therapeutic Ultrasound

ABSTRACT Remote, noninvasive chemical activation of bioactive molecules holds transformative potential for both biomedical research and therapeutic applications. Here, we report a deboronative hydroxylation reaction triggered by therapeutic ultrasound (termed dBus), in which boronic acid moieties are selectively converted into hydroxyl groups under clinically relevant, biocompatible conditions. We demonstrate that dBus enables spatiotemporally precise activation of diverse functional molecules, including fluorophores, bioactive small molecules, covalent labeling probes, peptides, and proteins, in both cellular systems and living animals. Mechanistic studies identify hydroxyl radicals, generated via ultrasound‐induced acoustic cavitation, as the reactive species driving this transformation. Notably, dBus facilitates ultrasound‐controlled prodrug activation in tumor‐bearing mice, resulting in significant tumor growth inhibition without systemic toxicity. With its simplicity, compatibility with existing ultrasound platforms, and broad molecular scope, dBus establishes a generalizable chemical foundation for noninvasive therapeutic intervention, precision diagnostics, and spatially resolved biological modulation.