EWVDV-Mediated Platelet-Targeting Nanoparticles for the Multimodal Imaging of Thrombi at Different Blood Flow Velocities

BACKGROUND: There have been many recent reports of molecular probes for thrombi but with unsatisfactory in vivo targeting effects, which could be related to the blood flow velocity in vivo. Therefore, it is worth explaining the relationship between the targeting effect and the blood flow velocity. METHODS AND MATERIALS: In this study, we constructed a platelet-targeting nanoparticle (NP) based on EWVDV for targeting P-selectin combined with the phase transition material perfluorohexane and India ink to achieve the multimodal imaging of thrombi. We studied the targeting effect of the NPs for rabbit blood thrombi under different flow velocities simulating blood flow velocities in vivo. RESULTS: The results show the successful fabrication of NPs with the ability to undergo a phase transition via low-intensity focused ultrasound irradiation to achieve ultrasound imaging and with a high binding affinity for activated platelets. In vitro, low flow velocities (20 cm/s) hardly affected the targeting effect of the NPs, while moderate flow velocities (40 cm/s) reduced the number of NPs that target thrombi by 52.6% comparing to static fluid (0 cm/s). High flow velocities (60 cm/s) greatly reduced the targeting effect of the NPs by 83.5%. CONCLUSION: These results can serve as a reference for the design of NPs targeting thrombi at different sites and in different blood vessel types according to the blood flow velocity, thereby establishing a foundation for in vivo experiments.