Ultrasound‐controlled drug release and drug activation for cancer therapy

Abstract

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.

Mechano‐Nanoswitches for Ultrasound‐Controlled Drug Activation

“…Meanwhile, one of the most longstanding challenges for transferring mechanochemistry to therapeutic ultrasound applications is to find a window of opportunity to activate the desired compounds while minimizing unwanted tissue damage. [ 24 ] We believe this proof‐of‐concept approach provides a blueprint for constructing drug activation nanoparticle systems with external control of ultrasound. With this approach, we conceived of a future pharmacotherapy that could have a well‐regulated activity that might avoid systemic side effects.…”

Low-Intensity Focused Ultrasound Technique in Glioblastoma Multiforme Treatment

“…These include expansions and contractions during the compression and rarefaction phases of the ultrasound pressure wave, respectively, as well as oscillations that require energy of lower magnitude compared to HIFU ( 12 , 31 ). These behaviors, such as oscillations, are often described as acoustic cavitation or simply cavitation ( 31 – 33 ). Cavitation can be classified as either stable or inertial, dependent on the acoustic pressure applied ( 12 , 19 , 33 ).…”

“…These behaviors, such as oscillations, are often described as acoustic cavitation or simply cavitation ( 31 – 33 ). Cavitation can be classified as either stable or inertial, dependent on the acoustic pressure applied ( 12 , 19 , 33 ). MBs oscillations are rather stable, linear, and symmetric at low ultrasonic pressures generating acoustic emissions at harmonics of the driving frequency while an increase in pressure leads to non-linear oscillations generating subharmonic and ultra-harmonic emissions ( 12 , 32 ).…”

The Phytochemical Potential for Brain Disease Therapy and the Possible Nanodelivery Solutions for Brain Access

“…Loading of its cargo usually employs the intrinsic properties of the targeted drug formula, such as electronic charges or water solubility. Upon administration, release-at-site is also required for a successful nanomedicine ( 83 ). To achieve efficient controlled release, specific conditional stimulus-responsive mechanisms are implemented.…”