Abstract
The Arg–Gly–Asp (RGD) peptide sequence was conjugated to poly (lactid acid), (PLA), microcapsules. These hollow, biodegradable PLGA microcapsules were developed in our laboratory for use as ultrasound contrast agents. By modifying the surface of the agent with a targeting ligand, it can be targeted to a specific address within the body. This application is ideal for both targeted imaging and/or targeted drug delivery. Integrins are membrane-spanning proteins in cells that play a vital role in cell attachment and many other processes. The RGD peptide sequence targets integrins expressed during angiogenesis, α vβ 3 and α vβ 5. The integrins specific to angiogenesis are more active during cancer and can be used as receptors for the RGD-conjugated contrast agents. Although the generic RGD sequence is not specific to only α vβ 3 and α vβ 5 integrins, it is an excellent candidate for proof of concepts studies such as described here. Preliminary in vitro results indicate that the modified capsules remain highly echogenic (maximum enhancement of 20 dB in vitro) and adhere specifically to a breast cancer cell line MDA-MB-231 in static experiments. However, no adherence is seen with either unmodified capsules (negative control), or when cells that have been pre-saturated with RGD ligand are contacted with modified capsules (positive control). Specific targeting of ultrasound contrast agents could lead the way to imaging as a method for discrimination of malignant from benign.
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