Low-Intensity Focused Ultrasound-Responsive Phase-Transitional Nanoparticles for Thrombolysis without Vascular Damage: A Synergistic Nonpharmaceutical Strategy

Multimodal molecular imaging has shown promise as a complementary approach to thrombus detection. However, the simultaneous noninvasive detection and lysis of thrombi for cardiovascular diseases remain challenging. Herein, a perfluorohexane (PFH)-based biocompatible nanostructure was fabricated, namely, as-prepared Fe3O4-poly(lactic-co-glycolic acid)-PFH-CREKA nanoparticles (NPs), which combine phase transition (PT) thrombolysis capabilities with properties conducive to multimodal imaging. This well-developed PT agent responded effectively to low-intensity focused ultrasound (LIFU) by triggering the vaporization of liquid PFH to achieve thrombolysis. The presence of the CREKA peptide, which binds to the fibrin of the thrombus, allows targeted imaging and efficacious thrombolysis. Then, we found that, compared with thrombolysis using a non-phase-transition agent, PT thrombolysis can produce a robust decrease in the thrombus burden regardless of the acoustic power density of LIFU. In particular, the reduced...