RGD-Tagged Microbubbles Generated by Versatile Fabrication Protocols for In Vitro Cell Targeting and In Vivo Mouse Imaging of Tumor Vascularization
By using an organic framework to fabricate functional biomaterials, novel design and advanced biomedical applications of polymeric microbubbles for in vivo targeting and disease-oriented imaging of tumor vascularization can be developed. The present study describes novel synthetic protocols to fabricate RGD (Arginine-Glycine-Aspartic)-tagged αvβ3-targeted ultrasound microbubbles. The microbubbles were synthesized by emulsion polymerization techniques. Two types of microbubbles (MBs-1 and MBs-2) were obtained via biotin-streptavidin conjugation to poly(butyl cyanoacrylate) microbubbles (MBs-0) obtained by one-step synthesis in reverse order. The size distributions and surface zeta potentials were characterized. The results showed that the sizes of the MBs-2 were larger than that those of the MBs-1, and the MBs-2 showed decreased charge compared to MBs-1. In cell targeting studies, MBs-2 exhibited relatively stronger targeting affinity for αvβ3 integrins, while MBs-1 showed weaker targeting capability. Furthermore, in vivo mice imaging using MBs-2 for intravenous injection exhibited an obvious and sustained signal increase, which revealed the accumulative of MBs-2 anchoring in tumor. Hence, MBs-2 have been proven to be a promising candidate for using as ultrasound contrast agents for the early diagnosis of αvβ3-overexpressing malignant tumors, including breast cancer.
危险品化学品经营许可证（带存储）