Experimental study on ultrasound/near-infrared dual-mode imaging and thrombolysis in vitro of phase-change mesoporous silicon nanoprobe / 中华超声影像学杂志

ABSTRACT

Objective:To explore the potential of thrombus-targeted nanoprobes for ultrasound/near-infrared bimodal imaging and their synergistic therapeutic effects on thrombosis in vitro.Methods:Nanoprobes loaded with arginine-glycine-aspartate peptide (RGD), perfluoropentane (PFP) and indocyanine green (ICG) were prepared by ultrasonic vibration and carbodiimide method with mesoporous silica nanoparticle (MSN) as the carrier. The probe morphology was observed by scanning and transmission electron microscopy. The loading of RGD and ICG was detected by Bicinchoninic Acid Assay (BCA) and UV-Visible-NIR spectroscopy respectively. The imaging performance and photothermal response of the nanoprobe under near infrared light (NIR) irradiation were studied in vitro. Its biological safety was tested by cytotoxicity test and hemolysis test. The phase transformation was studied under ultrasound and NIR irradiation. The nanoprobe was incubated with fresh arterial thrombus, and its target-seeking ability was observed by frozen section. Ultrasound and NIR irradiation were used to evaluate its thrombolytic ability by the weight changes of thrombus before and after irradiation.Results:The prepared nanoprobe had regular morphology and uniform size. The particle diameter was (156.83±5.05)nm, and the surface potential was (11.47±0.25)mV. The RGD coupling rate was (77.67±4.50)%, which could mediate the targeting of nanoprobe to fresh extracorporeal arterial thrombus. UV-Visible-NIR spectroscopy confirmed the successful loading of ICG, and its encapsulation rate was (80.47±0.05)%. After ultrasound and NIR irradiation, the nanoprobe could undergo acoustically induced phase transition, thermally induced phase transition and enhance the ultrasonic development effect. With the increase of the concentration of the nanoprobe solution, the NIR signal gradually increased, and the temperature rose in a concentration-dependent and intensity-dependent manner after NIR irradiation. The cytotoxicity test and hemolysis test showed that the nanoprobe had good biological safety, and it could play a thrombolytic role under the combined irradiation of ultrasound and NIR, and the weight of thrombus was significantly reduced after the treatment ( P<0.01). Conclusions:In this study, the nanoprobe (RGD/ICG/PFP@MSN) were successfully prepared possesses excellent dual mode imaging capabilities of ultrasound and NIR, excellent phase transition ability and photothermal conversion efficiency, as well as efficient targeted penetration and therapeutic effects against thrombosis. This study provides strong in vitro experimental evidence and new strategies for the integration of diagnosis and treatment of thrombotic diseases under the cooperation of ultrasound and NIR.