Multimodal and multifunctional nanoparticles with platelet targeting ability and phase transition efficiency for the molecular imaging and thrombolysis of coronary microthrombi

Recently, coronary microthrombosis has received attention owing to its involvement in the pathophysiological process of no-reflow after acute myocardial ischemia/reperfusion. Due to the small size of coronary microthrombi, there are no precise detection and treatment methods available in the clinic so far. In experimental study, bimodal molecular probes for both detecting and dissolving coronary microthrombi have not yet been reported. In this study, multimodal and multifunctional PLGA-cRGD-PFH-ICG NPs (PLGA: poly(lactic- co -glycolic) acid, cRGD: cyclic arginine-glycine-aspartic acid, PFH: perfluorohexane, ICG: indocyanine green, NPs: nanoparticles) were constructed through a three-step emulsification process, and the corresponding physical and chemical characteristics of the NPs were also tested. The in vitro and in vivo experiments showed that PLGA-cRGD-PFH-ICG NPs could bind to the activated platelets of coronary microthrombi through cRGD and could achieve bimodal molecular imaging (photoacoustic and near-infrared fluorescence) through ICG. Moreover, the PLGA-cRGD-PFH-ICG NPs could permeate more deeply into the thrombus than other common NPs before being triggered by low-intensity focused ultrasound (LIFU), and thrombolysis was carried out through the cavitation effect of PFH after triggering by LIFU. In summary, PLGA-cRGD-PFH-ICG NPs, constructed with safe and approved materials, serve as an excellent theranostic contrast agent that paves the way for the clinical diagnosis and treatment of coronary microthrombosis. In this article, we constructed PLGA-cRGD-PFH-ICG NPs through emulsification process and then the bi-modal imaging of coronary microthrombi in ischemia/reperfusion rat model and thrombolysis of clots in vitro were both successfully completed by these NPs.