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

Jianwu Xie¹, Zhimin Shen², King CP Li^1,3, 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 α_vβ₃. Our group is involved in the development of molecular imaging probes and drug delivery systems targeting α_vβ₃. Based on extensive lead optimization study with the integrin antagonist compounds, we have developed a new generation of integrin α_vβ₃ compound (IA) which has superior binding affinity to α_vβ₃. 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_vβ₃ was observed. These ITNPs also were rapidly taken up by cells that express α_vβ₃. 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 α_vβ₃, cancer, angiogenesis