Receptor-Targeted Nanoparticles for In Vivo Imaging of Breast Cancer

• Authors: Lily Yang, Emory University; Xianghong Peng, Emory University; Y. Andrew Wang, Department of Ocean Nanotech, LLC, Springdale, Arkansas; Xiaoxia Wang, Emory University; Zehong Cao, Emory University; Chunchun Ni, Emory University; Prasanthi Karna, Emory University; Xinjian Zhang, Department of Chemistry, Georgia State University, Atlanta, Georgia.; William C Wood, Emory University; Xiaohu Gao, Emory University; Shuming Nie, Emory University; Hui Mao, Emory University
• Journal Title: Clinical Cancer Research
• Volume: Volume 15, Number 14
• Publisher: American Association for Cancer Research | 2009-07-15, Pages 4722-4732
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1078-0432.CCR-08-3289
• Subjects: Chemistry, Physical; Chemistry, Biochemistry
• Keywords: magnetic resonance imaging; near infrared optical imaging; molecular imaging; magnetic iron oxide nanoparticle; urokinase plasminogen receptor; breast cancer

Abstract

Purpose Cell surface receptor-targeted magnetic iron oxide (IO) nanoparticles provide molecular magnetic resonance imaging (MRI) contrast agents for improving specificity of the detection of human cancer. Experimental design The present study reports the development of a novel targeted IO nanoparticle using a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator conjugated to IO nanoparticles (ATF-IO). This nanoparticle targets urokinase plasminogen activator receptor (uPAR), which is overexpressed in breast cancer tissues. Results ATF-IO nanoparticles are able to specifically bind to and be internalized by uPAR-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing subcutaneous and intraperitoneal mammary tumors leads to the accumulation of the particles in tumors, generating a strong MRI contrast detectable by a clinical MRI scanner at a field strength of 3 Tesla. Target specificity of ATF-IO nanoparticles demonstrated by in vivo MRI is further confirmed by near infrared (NIR) fluorescence imaging of the mammary tumors using NIR dye-labeled ATF peptides conjugated to IO nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared to those receiving non-targeted IO nanoparticles. Conclusions Our results suggest that uPAR-targeted ATF-IO nanoparticles have potential as molecularly-targeted, dual modality imaging agents for in vivo imaging of breast cancer.