Drug delivery system based on nanobubbles

Ultrasound (US) medical technology is widely used due to its advantages of safety, speed, and low cost. With the rapid development of biomedical nanotechnology, micro/nanobubbles, as US contrast agents, are not only valuable in US imaging diagnosis but also show broad application prospects in drug delivery. Nanobubbles (NBs) have more advantages as drug delivery systems (DDSs) due to their smaller size and longer circulation time compared with microbubbles. In this review, the fundamentals of NBs, including classification, stability mechanism, and preparation methods are summarized. Then, the strategies of a DDS based on NBs, including direct delivery, codelivery, target delivery, and stimuli‐responsive delivery are reviewed and discussed. The three main applications of NBs‐based DDSs, namely tumor theranostics, brain drug delivery, and vascular disease theranostics were highlighted. The challenges and future directions of the NBs‐based DDSs are also considered and discussed. Based on a comprehensive overview of the nanobubbles (NBs) fundamentals, the strategies using NBs for novel drug delivery are discussed. Applications, including tumor theranostics through enhanced permeability and retention, brain drug delivery by blood−brain barrier opening, and vascular theranostics are presented. Current challenges in the combination of NBs and ultrasound for drug delivery and the corresponding mechanisms that need to be addressed are proposed.