Phase Transition Nanoparticles as Multimodality Contrast Agents for the Detection of Thrombi and for Targeting Thrombolysis: in Vitro and in Vivo Experiments

Thrombotic disease is extremely harmful to human health, and early detection and treatment can improve the prognosis and reduce mortality. Multimodal molecular imaging can provide abundant information about thrombi, but to date, few studies have used multimodal and multifunctional nanoparticles (NPs) for thrombus detection and for targeting thrombolysis. In this study, phase transition multimodal and multifunctional NPs (EWVDV-Fe-Ink-PFH NPs) were constructed for the first time using a three-step emulsification and carbodiimide method, and the physical and chemical properties of the NPs were investigated. The targeting abilities of the NPs and multimodal imaging, that is, photoacoustic, magnetic resonance, and ultrasound imaging, were successfully achieved in vitro and in vivo. The ability of the EWVDV peptide on the NPs to effectively target the P-selectin of thrombi was confirmed by multimodal imaging and pathology, and the penetration depths of the NPs into the thrombi were far deeper than the previously reported depths. Moreover, a perfluorohexane (PFH) phase transition induced by low-intensity focused ultrasound irradiation enabled the EWVDV-Fe-Ink-PFH NPs to cause thrombolysis in vitro. In summary, EWVDV-Fe-Ink-PFH NPs are a theranostic contrast agent that will provide a simple, effective, and noninvasive approach for the diagnosis and treatment of thrombosis.