Ultrasound-driven microbubble motors for targeted myocardial ischemia-reperfusion injury treatment

Myocardial ischemia-reperfusion injury (MIRI) is a secondary pathological process that occurs after restoration of blood flow during the treatment of acute myocardial infarction. The effective prevention of MIRI is pivotal for optimizing therapeutic efficacy and improving long-term patient outcomes. In this study, we developed an ultrasound-driven, multilevel targeted bionic microbubble motor (CsA@NM-MBs motors) that can break through the vascular endothelial and cell membrane barriers to achieve precise, targeted drug delivery. The CsA@NM-MBs motors were coated with a neutrophil membrane, a highly biocompatible membrane with natural inflammatory targeting abilities, enabling active homing to damaged areas. Upon application of an external ultrasound field, the CsA@NM-MBs motors actively crossed the vascular endothelial barrier and reached the myocardial tissue in the MIRI area with precision. With the aid of ultrasound-targeted microbubble destruction (UTMD) technology, acoustic pores are formed on the cell membrane, enabling it to break through the cell barrier. The driving force generated by the explosion enables CsA to be delivered into cells, thereby achieving safe and efficient drug release. This ultrasound-driven cell membrane biomimetic multilevel targeting strategy significantly enhanced the enrichment and delivery efficiency of CsA at the injury site, providing a new approach for the treatment of MIRI.