The long term goal of the present proposal is to develop a nanoparticle that can be targeted to tissues with specific molecular signatures. Inclusion of a contrast agent (Iron Oxide for MRI) within the nanoparticle would therefore facilitate non-invasive imaging of specific biochemical properties within tissues in-vivo. The present proposal is focused on investigating if a nanoparticle based contrast agent can be efficiently targeted to cells with specific molecular characteristics. Two well-characterized molecular targets will be investigated. The first involves targeting to endothelial cells that express alpha-V-beta-3 and alpha-V-beta-5 integrins using the sequence CDCRGDCFC. Expression of these integrins is a hallmark of endothelial cells within angiogenic vasculature (e.g. within tumors). Similarly, we will target tissues (endothelial cells and tumors) that are undergoing tissue remodeling. Since expression of the metalloproteases MMP-2 and MMP-9 is characteristic of cells that need to migrate through the extracellular matrix or basement membrane, inclusion of the CTTHWGFTLC within a nanoparticle will target nanoparticles to tumors and tumor vasculature that typically express these proteases. It is anticipated that the results from the proposed studies will provide the foundation for future development of these novel nano-structure-based strategies for non-invasive in vivo imaging of specific biochemical events.
