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Author Notes:

*Correspondence: Lily Yang, MD, PhD, Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, C-4088, 1365 C Clifton Road NE, Atlanta, GA 30322. Phone: (404) 778-4269; Fax: (404) 778-5530; E-mail: Lyang02@emory.edu; Or Hui Mao, PhD, Department of Radiology, Emory Center for Systems Imaging, Emory University School of Medicine, 1841 Clifton Road, Atlanta, GA 30329. Phone: (404) 712-0357; Fax: (404) 712-5948; E-mail: hmao@emory.edu

Current address: Department of Bioengineering, University of Washington, Seattle, Washington.

These authors contributed equally to the studies in this manuscript.

Acknowledgments We thank Dr. Anthea Hammond for her critical editing of the manuscript, Dr. Mark W. Dewhirst for kindly providing us with luciferase gene–stable 4T1 cell line, Drs. Adam Marcus and Katherine Schafer-Hales in the Cell Imaging Core of the Winship Cancer Institute for their assistance in confocal microscopy, and Dr. Hongwei Duan for his help with zeta potential and particle size analysis.

Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed.

Subjects:

Research Funding:

National Cancer Institute : NCI

Keywords:

  • magnetic resonance imaging
  • near infrared optical imaging
  • molecular imaging
  • magnetic iron oxide nanoparticle
  • urokinase plasminogen receptor
  • breast cancer

Receptor-Targeted Nanoparticles for In Vivo Imaging of Breast Cancer

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Journal Title:

Clinical Cancer Research

Volume:

Volume 15, Number 14

Publisher:

, Pages 4722-4732

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2009 American Association fo Cancer research

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