Ultrasound-controlled drug release and drug activation for cancer therapy

Traditional chemotherapy suffers from severe toxicity and side effects that limit its maximum application in cancer therapy. To overcome this challenge, an ideal treatment strategy would be to selectively control the release or regulate the activity of drugs to minimize the undesirable toxicity. Recently, ultrasound (US)-responsive drug delivery systems (DDSs) have attracted significant attention due to the non-invasiveness, high tissue penetration depth, and spatiotemporal controllability of US. Moreover, the US-induced mechanical force has been proven to be a robust method to site-selectively rearrange or cleave bonds in mechanochemistry. This review describes the US-activated DDSs from the fundamental basics and aims to present a comprehensive summary of the current understanding of US-responsive DDSs for controlled drug release and drug activation. First, we summarize the typical mechanisms for US-responsive drug release and drug activation. Second, the main factors affecting the ultrasonic responsiveness of drug carriers are outlined. Furthermore, representative examples of US-controlled drug release and drug activation are discussed, emphasizing their novelty and design principles. Finally, the challenges and an outlook on this promising therapeutic strategy are discussed.