Ultrasound-activated mechanochemical reactions for controllable biomedical applications

Intramolecular bonds in small organic molecules, macromolecules, and organic-inorganic hybrids are broken or formed by ultrasound-activated mechanical force that can be applied with spatial and temporal precision for contactless external control of mechanochemical reactions. Ultrasound featuring non-invasiveness, high tissue penetration, and spatiotemporal controllability has shown great potential in controlling the activation of mechanochemical reactions such as chemical bond scission, natural enzyme activation, and catalytic radical generation for targeted drug or gene therapy. Here, we comprehensively summarize the latest research and future trends in ultrasound-activated mechanochemical reactions for smart biomedical applications. First, the mechanism of ultrasound-activated mechanochemical reactions will be outlined. Then, the types of mechanochemical reactions will be carefully discussed. After that, the representative biomedical applications have been summarized from a unique perspective. Finally, we systematically emphasize the current challenges and future outlooks to guide the rational design of ultrasound-activated drug release over conventional drug-loaded therapies. We believe that this review will substantially facilitate the progression and widespread utilization of ultrasound-activated mechanochemical reactions in biomedical applications.