Journal
ACS NANO
Volume 13, Issue 3, Pages 3387-3403Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b09277
Keywords
thrombolysis; CREKA peptide; low-intensity focused ultrasound; phase transition; multimodal imaging
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Funding
- National Natural Science Foundation of China [81571663, 81630047, 81471713]
- Construction Program of Chongqing University Innovation Team [CXTDG201602007]
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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 energy for LIFU-responsive PT during the lysis process guarantees the superior safety of PT thrombolysis. After injecting the NPs intravenously, we demonstrated that this lysis process can be monitored with ultrasound and photoacoustic imaging in vivo to evaluate its efficacy. Therefore, this nonpharmaceutical strategy departs from routine methods and reveals the potential use of PT thrombolysis as an effective and noninvasive alternative to current thrombolytic therapy.
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