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Development of peptide conjugated Superparamagnetic Iron Oxide (SPIO) Nanoparticles for Targeted MR Imaging and Therapy of Pancreatic Cancer

L. Yang, H. Mao, Z. Cao, A. Wang, X. Peng, X. Wang, P. Karna, G. Adams, Q. Yuan, C. Staley, W.C. Wood, S. Nie and X. Gao
Emory University, US

superparamagnetic iron oxide nanoparticles, tumor imaging, pancreatic cancer, tumor targeted magnetic iron oxide particles

We have engineered superparamagnetic iron oxide (IO) nanoparticles targeted to urokinase plasminogen receptors (uPAR), which is highly expressed in tumor cells, intratumoral fibroblasts and tumor endothelial cells and can also be internalized by cells. IO nanoparticles with highly uniformed core sizes were coated with amphiphilic polymers and conjugated to peptides containing a uPAR binding region of uPA (ATF-IO). We demonstrated that ATF-IO nanoparticles specifically bound to human pancreatic cancer cells evidenced by significantly shortened T2 in ATF-IO-treated cells but not in unconjugated IO or GFP-IO. MRI scan of nude mice bearing orthotopic pancreatic tumors before IO particle injection showed bright signals in the tumor areas. However, after systemic delivery of ATF-IO particles into the mouse, we observed a significant signal drop in those areas, suggesting a T2 shortening effect of selective accumulation of ATF-IO in pancreatic cancers. However, MRI images from a tumor-bearing mouse injected with unconjugated IO particles did not show a significant T2 effect in the tumor area. Our results demonstrated that ATF-IO nanoparticles have great potential for the development of multi-functional nanoparticles for in vivo imaging and therapy of pancreatic cancer.

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