Application of Targeted Nano-Bubble Ultrasound Contrast Agent in the Detection of Arterial Intima Inflammation in Rats

Abstract

Tumor-specific antibodies or ligands were connected to the surface of nano-bubbles to form a targeted nano-bubble ultrasound contrast agent (UCA), which can accumulate in tumor tissues, enhance tumor tissue visualization, and realize extravascular disease detection and ultrasound molecular imaging. In this research, the positive and negative charges were attracted to promote the self-assembly connection between the targeted vascular endothelial growth factor (VEGF) antibody and the envelope surface of the nano-bubble, thereby obtaining a tumor-specific targeted nano-bubble UCA. Then, from the basic characterization, in vivo and in vitro ultrasound contrast performance analysis, a rat model of arterial intima inflammation in vivo was constructed. 16 Wistar rats were screened and divided into a control group and a contrast-enhanced ultrasound group. The imaging performance of the targeted molecules was analyzed by preparing an UCA. in vitro contrast-enhanced ultrasound found that the contrast intensity of self-made targeted nano-bubbles was greatly affected by concentration, but there was no linear relationship between the two. in vivo experiments were performed to observe rat liver contrast. The results showed that the contrast intensity and contrast time of the targeted nano-bubbles in vivo were greatly affected by the dose, and the stability in vivo was lower than the stability in vitro. Immunohistochemical tests found that P-selectin was expressed in large amounts in the intima of damaged blood vessels. Compared with ordinary contrast agents, the prepared targeted nano-UCA after modeling can enhance the video intensity of the inner membrane (P <0.05) and prolong the imaging time (P <0.05). It suggested that the contrast agent can specifically bind to P-selectin on the surface of vascular endothelial cells, and it was expected to be used for the detection of early inflammatory lesions in atherosclerotic diseases.