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Author Notes:

Author 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, Georgia 30322. Fax: (404) 778-5530. Email: lyang02@emory.edu.

Shuming Nie, PhD, Department of Biomedical Engineering, Emory University School of Medicine, 101 Woodruff Circle, Suite 2007B, Atlanta, Georgia 30322. Fax: (404) 727-3567. Email: snie@emory.edu.

L.Y. and H.M. contributed equally to this manuscript.

The authors thank Drs Jack Arbiser and Ming-Sound Tsao for MS1 and HPDE6 cell lines, Dr Robert Long for assisting in magnetic resonance imaging, Dr Young–seok Cho for helping with the chronic pancreatitis model, and Dr Anthea Hammond for editing the manuscript.

Y.A.W. discloses that he is the president and principal scientist of Ocean Nanotech LLC.

The remaining authors disclose no conflicts.

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Research 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.

Molecular Imaging of Pancreatic Cancer in an Animal Model Using Targeted Multifunctional Nanoparticles

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Journal Title:

Gastroenterology

Volume:

Volume 136, Number 5

Publisher:

, Pages 1514-25.e2

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2009 by the AGA Institute

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