title: Tumor angiogenic endothelial cell targeting by a novel integrin-targeted nanoparticle.
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 alphav beta3. Our group is involved in the development of molecular imaging probes and drug delivery systems targeting alphav beta3. Based on extensive lead optimization study with the integrin antagonist compounds, we have developed a new generation of integrin alphav beta3 compound (IA) which has superior binding affinity to alphav beta3. Utilizing this IA as a targeting agent, we have developed a novel integrin-targeted nanoparticle (ITNP) system for targ alphav beta3 was observed. These ITNPs also were rapidly taken up by cells that express alphav beta3. 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.
authors.affiliation: Molecular Imaging Laboratory, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Xie
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shen
authors.forename: King C P
authors.initials: KC
authors.lastname: Li
authors.forename: Narasimhan
authors.initials: N
authors.lastname: Danthi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D051379:Mice; D008809:Mice, Inbred C3H; D053758:Nanoparticles / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D039302:Integrin alphaVbeta3