Tumor angiogenic endothelial cell targeting by a novel integrin-targeted nanoparticle

Angiogenesis is an important process in cancer growth and metastasis. During the tumor angiogenic process, endothelial cells express various cell surface receptors which can be utilized for molecular imaging and targeted drug delivery. One such protein receptor of interest is the integrin α(v)β(3). Our group is involved in the development of molecular imaging probes and drug delivery systems targeting α(v)β(3). Based on extensive lead optimization study with the integrin antagonist compounds, we have developed a new generation of integrin α(v)β(3) compound (IA) which has superior binding affinity to α(v)β(3). Utilizing this IA as a targeting agent, we have developed a novel integrin-targeted nanoparticle (ITNP) system for targeted drug delivery and imaging of cancer angiogenesis. When multiple copies of the IA were conjugated onto the nanoparticle surface, strong and selective binding to the integrin α(v)β(3) was observed. These ITNPs also were rapidly taken up by cells that express α(v)β(3). The ITNPs accumulated in the angiogenic vessels, after systemic administration in a murine squamous cell carcinoma model. This novel intergrin targeted ITNP platform will likely have an application in targeted delivery of drugs and genes in vivo and can also be used for molecular imaging.