Abstract
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.
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