This NIH SBIR project intends to develop a new generation of iron oxide nanoparticles as target specific MRI contrast agents for early detection of breast cancer. Recent advances in iron oxide synthesis in organic solvents at elevated reaction temperature allow the preparation of size tunable and monodisperse particles. These hydrophobic nanoparticles can be converted to water soluble and biolinkable nanoparticles. Our extensive research has demonstrated that these nanoparticles are very stable and can be conjugated to affinity ligands for target specific imaging. Most important, they show little liver uptake but prominent renal uptake. Such phenomenon is vastly different from all literature reported results as all of them have high reticuloendothelial system (RES) uptake in the liver and spleen and none of them has renal clearance due to the relatively large size and agglomeration in vivo. In this Phase I project, we will perform rigorous in vitro, in vivo and ex vivo characterization of various affinity ligand modified iron oxide nanoparticles for targeting integrin 1v23 that is aberrantly expressed on tumor vasculature and invasive tumor cells in breast cancer. In Phase II, focus will be shifted to improving the sensitivity, further reducing reticuloendothelial system (RES) uptake, and studying the toxicity of the proposed probes. The final deliverable of this project is a highly sensitive, clinically applicable MR imaging probe for breast cancer diagnostics.

Public Health Relevance

Breast cancer is the second leading cause of death in the United States. In 2007, about 1,444,920 new cancer cases were expected to be diagnosed, and about 559,650 Americans were expected to die of cancer-more than 1,500 people per day. Enhancing early stage cancer diagnostics is very critical to increase the survival rate of patients. The proposed iron oxide nanoparticle probe as target specific MRI contrast enhancer will provide a platform to detect tumor in its early stage.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
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Special Emphasis Panel (ZRG1-SBMI-T (10))
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Beylin, David M
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Ocean Nanotech, LLC
United States
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Jang, Eue-Soon; Shin, June-Ho; Ren, Gang et al. (2012) The manipulation of natural killer cells to target tumor sites using magnetic nanoparticles. Biomaterials 33:5584-92
Bu, Lihong; Xie, Jin; Chen, Kai et al. (2012) Assessment and comparison of magnetic nanoparticles as MRI contrast agents in a rodent model of human hepatocellular carcinoma. Contrast Media Mol Imaging 7:363-72
Zhang, Fan; Huang, Xinglu; Zhu, Lei et al. (2012) Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles. Biomaterials 33:5414-22