Molecular Imaging of Pancreatic Cancer in an Animal Model Using Targeted Multifunctional Nanoparticles
Received 21 February 2008; accepted 8 January 2009. published online 16 January 2009.
Background & Aims
Identification of a ligand/receptor system that enables functionalized nanoparticles to efficiently target pancreatic cancer holds great promise for the development of novel approaches for the detection and treatment of pancreatic cancer. Urokinase plasminogen activator receptor (uPAR), a cellular receptor that is highly expressed in pancreatic cancer and tumor stromal cells, is an excellent surface molecule for receptor-targeted imaging of pancreatic cancer using multifunctional nanoparticles.
Methods
The uPAR-targeted dual-modality molecular imaging nanoparticle probe is designed and prepared by conjugating a near-infrared dye-labeled amino-terminal fragment of the receptor binding domain of urokinase plasminogen activator to the surface of functionalized magnetic iron oxide nanoparticles.
Results
We have shown that the systemic delivery of uPAR-targeted nanoparticles leads to their selective accumulation within tumors of orthotopically xenografted human pancreatic cancer in nude mice. The uPAR-targeted nanoparticle probe binds to and is subsequently internalized by uPAR-expressing tumor cells and tumor-associated stromal cells, which facilitates the intratumoral distribution of the nanoparticles and increases the amount and retention of the nanoparticles in a tumor mass. Imaging properties of the nanoparticles enable in vivo optical and magnetic resonance imaging of uPAR-elevated pancreatic cancer lesions.
Conclusions
Targeting uPAR using biodegradable multifunctional nanoparticles allows for the selective delivery of the nanoparticles into primary and metastatic pancreatic cancer lesions. This novel receptor-targeted nanoparticle is a potential molecular imaging agent for the detection of pancreatic cancer.
Reprint requests Address requests for reprints to: Lily Yang, MD, PhD, Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, C-4088, 1365 C Clifton Road NE, Atlanta, Georgia 30322. fax: (404) 778-5530
Shuming Nie, PhD, Department of Biomedical Engineering, Emory University School of Medicine, 101 Woodruff Circle, Suite 2007B, Atlanta, Georgia 30322. fax: (404) 727-3567
Conflicts of interest Y.A.W. discloses that he is the president and principal scientist of Ocean Nanotech LLC. The remaining authors disclose no conflicts.
Funding Supported by the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology of the National Institutes of Health Center of Cancer Nanotechnology Excellence (CCNE, U54 CA119338-01) and by seed grants from the Golfers Against Cancer Foundation, The Friends For An Early Breast Cancer Test, and EmTech Bio, Inc.
ABSTRACT
Molecular Imaging of Pancreatic Cancer in an Animal Model Using Targeted Multifunctional Nanoparticles