Remote Molecule Activation in Living Mice Triggered by Therapeutic Ultrasound
Shengnan Qin1, Xuan Liang1, Yufei Di1
1Synthetic and Functional Biomolecules Center, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
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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.
