Abstract
Introduction: Thrombotic microvascular obstruction (MVO) poses a diagnostic challenge due to the lack of specific imaging techniques in clinical practice. This study introduces a novel ultrasound imaging method that utilizes gold nanoparticles (AuNPs) modified with the GPIIb/IIIa-targeting peptide Arg-Gly-Asp (RGD) to enhance the contrast of ultrasound imaging for microembolization. Methods: Targeted gold nanoparticles (RGD-AuNPs) and untargeted gold nanoparticles (GSH-AuNPs) were synthesized using the glutathione reduction method from chloroauric acid. A rat model of MVO was established by infusing microthrombi into the left hindlimb via the right femoral artery. The rats were randomly assigned to receive either RGD-AuNPs or GSH-AuNPs injected via an angiocatheter. Ultrasound imaging was performed on the left hindlimb for three hours at five-minute intervals, and the average video intensity of the images was measured. Histological staining and immunohistochemistry were performed to validate the co-localization of microthrombi and RGD-AuNPs. Results: In the RGD-AuNPs+MVO group, enhanced ultrasound signals were visible at 15 minutes and progressively increased over three hours. The average video intensity in this group was approximately three times higher than that in the GSH-AuNPs+MVO group (11.88±3.68 vs. 3.39±2.67, p<0.001). No significant difference in average video intensity was observed between the GSH-AuNPs+MVO group and the GSH-AuNPs control group (3.39±2.67 vs. 3.50±2.09, p>0.05), or between the GSH-AuNPs control group and the RGD-AuNPs control group (3.50±2.09 vs. 2.95±2.18, p>0.05). Histological staining and immunohistochemistry confirmed the co-localization of microthrombi and RGD-AuNPs. Conclusions: Gold nanoparticles modified with the RGD peptide effectively enhance the signal of ultrasound imaging, enabling targeted imaging of thrombotic microvascular obstruction. This approach holds promise for improving the diagnosis and monitoring of MVO in clinical settings.
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