Ultrasound activated bowl-like nanomotors release nitric oxide for enhanced thrombus therapy

Abstract

Conventional thrombolytic therapies are often hampered by insufficient targeting accuracy, elevated risks of bleeding, and poor efficacy against aged thrombi. To overcome these limitations, we developed an ultrasound (US)-activated nitric oxide (NO)-releasing nanomotor, termed AB-LC, for improved thrombus treatment. The system is constructed from bowl-shaped gold nanoparticles (AB) loaded with L-arginine as a NO donor and functionalized with the fibrin-targeting peptide cRGD. Upon US irradiation, the asymmetric bowl-like structure facilitates enhanced accumulation and penetration into thrombotic regions by leveraging shear stress-induced propulsion. Simultaneously, under sonodynamic therapy (SDT), AB-LC generates reactive oxygen species (ROS), which promote the localized conversion of L-arginine into NO, thereby enabling vasodilation, antiplatelet aggregation, and fibrinolytic activity. By integrating SDT, asymmetric morphology-enhanced mobility, and NO-mediated multimodal thrombolysis, AB-LC effectively circumvents the side effects and recanalization challenges associated with traditional thrombolytic drugs. This platform thus provides a targeted, efficient, and safer alternative for thrombus management, opening a new avenue for precision nanomedicine in thrombosis therapy.