Tumor angiogenic endothelial cell targeting by a novel integrin-targeted nanoparticle
Authors Jianwu Xie, Zhimin Shen, King CP Li, Narasimhan Danthi
Published 15 October 2007 Volume 2007:2(3) Pages 479—485
Jianwu Xie1, Zhimin Shen2, King CP Li1,3, Narasimhan Danthi1
1Molecular Imaging Laboratory, Clinical Center and 2Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA; 3Department of Radiology, The Methodist Hospital, Houston, TX, USA
Abstract: 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 αvβ3. Our group is involved in the development of molecular imaging probes and drug delivery systems targeting αvβ3. Based on extensive lead optimization study with the integrin antagonist compounds, we have developed a new generation of integrin αvβ3 compound (IA) which has superior binding affinity to αvβ3. 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 αvβ3 was observed. These ITNPs also were rapidly taken up by cells that express αvβ3. 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.
Keywords: targeted nanoparticle, integrin αvβ3, cancer, angiogenesis