Nanodroplet-coated microbubbles used in sonothrombolysis with two-step cavitation strategy.

Thrombosis is a major cause of morbidity and mortality and sonothrombolysis is a promising method for treatment of thrombosis. However, the slow diffusion of the thrombolytic agents into the thrombus results in slow recanalization. Here, we design and fabricate nanodroplet-coated microbubbles (NCMBs) and use two-step cavitation strategy to accelerate the thrombolysis. The first cavitation of the NCMBs, cavitation and collapse of the microbubbles induced by the low frequency ultrasound, drives the nanodroplets on the shell into the thrombus, while the second cavitation, the phase-change and volume expansion of drug-loaded nanodroplets triggered by the high frequency ultrasound, loosens the thrombus by sono-porosity effect. This two-step cavitation of the NCMBs are verified using a fibrin agarose model, where a rapid diffusion of the thrombolytic agents is observed. Furthermore, the NCMBs reach much higher thrombolysis efficiency in both in vitro and proof-of-concept experiments performed with living mice. The nanodroplet-coated microbubbles is a promising diffusion medicines carrier for efficient drug delivery. This article is protected by copyright. All rights reserved.