Iron oxide nanoparticle probes for target specific MR molecular imaging

描述(由申请人提供)：NIH SBIR项目旨在开发新一代氧化铁纳米颗粒作为靶向特定的MRI造影剂，用于乳腺癌的早期检测。在有机溶剂中提高反应温度合成氧化铁的最新进展使制备尺寸可调的单分散粒子成为可能。这些疏水纳米颗粒可以转化为水溶性和可生物链接的纳米颗粒。我们广泛的研究表明，这些纳米粒子非常稳定，可以连接到亲和配体上进行靶向特异性成像。最重要的是，它们的肝脏摄取很少，但肾脏摄取明显。这种现象与所有文献报道的结果有很大的不同，因为它们都在肝脏和脾中有较高的网状内皮系统(RES)摄取，而由于体内相对较大的尺寸和聚集，它们都没有肾脏清除。在这个第一阶段的项目中，我们将对不同亲和配体修饰的氧化铁纳米颗粒进行严格的体外、体内和体外表征，以靶向在乳腺癌肿瘤血管和侵袭性肿瘤细胞上异常表达的整合素1v23。在第二阶段，重点将转移到提高灵敏度，进一步减少网状内皮系统(RES)摄取，并研究拟议的探针的毒性。该项目的最终成果是一种用于乳腺癌诊断的高灵敏度、临床适用的磁共振成像探头。与公共健康相关：乳腺癌是美国第二大死因。2007年，预计将诊断出约1,444,920例新的癌症病例，预计约有559,650名美国人死于癌症--每天超过1500人。加强对癌症的早期诊断是提高患者生存率的关键。所提出的氧化铁纳米粒子探针作为靶向特异性MRI对比剂将为肿瘤的早期检测提供一个平台。

DESCRIPTION (provided by applicant): 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.