The development of ultrasound-responsive microcapsule structures has resulted in several spatiotemporally controlled drug delivery systems for macromolecular cargoes, including proteins, nucleic acids, and even cells for biomedical applications. However, utilizing microcapsules to transport small molecular cargoes remains a challenge, because the leakage of drugs before ultrasound irradiation might cause side effects such as the undesired toxicity and the decrease of effective drug concentration at the target site. Herein, we present a novel strategy to tackle these shortcomings by employing nanodrugs which refers to nanoparticles coated with small molecule drugs. We showed that the drug leakage was prevented when encapsulating the nanodrug in microcapsules. Moreover, the fabricated drug delivery system was responsive not only to unfocused high-intensity ultrasound but also to the clinically relevant high-intensity focused ultrasound. Finally, as a proof of concept, we showed that the antibacterial activity of the nanodrug@Microcapsules could be activated by applying ultrasound in situ. These results may provide new insights into the development of ultrasound triggered small molecule drug delivery assisted by metallic nanoparticles.

超声响应微胶囊结构的发展导致了几种用于大分子货物的时空控制药物递送系统，包括蛋白质、核酸，甚至用于生物医学应用的细胞。然而，利用微胶囊运输小分子货物仍然是一个挑战，因为在超声照射之前药物的泄漏可能会导致副作用，例如不良毒性和靶位有效药物浓度的降低。在此，我们提出了一种通过使用纳米药物来解决这些缺点的新策略，纳米药物是指涂有小分子药物的纳米颗粒。我们表明，将纳米药物封装在微胶囊中时可以防止药物泄漏。而且，制造的药物输送系统不仅对非聚焦高强度超声有反应，而且对临床相关的高强度聚焦超声也有反应。最后，作为概念验证，我们表明纳米药物@微胶囊的抗菌活性可以通过应用超声波来激活原地。这些结果可能为金属纳米粒子辅助的超声触发小分子药物递送的发展提供新的见解。