SBIR Topic 252 - Magnetic Iron Oxide Nanoparticles for Imaging Enhancer

氧化铁磁性纳米粒子因其在生物医学研究中的广泛应用，具有高磁化值、大小可控、表面化学可控等优点，目前正受到广泛的研究。在有机溶剂中高温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。NIH SBIR项目旨在开发这种新一代的氧化铁纳米颗粒，作为胰腺癌检测的靶向特异性磁共振造影剂。 其具体目的是：1)制备具有不同表面配体(如COOH、NH2、生物素、链霉亲和素和免疫球蛋白)的氧化铁纳米颗粒试剂盒，用于靶向特异性MR1成像。每个纳米颗粒上的官能团的数量将被量化。 2)优化氧化铁纳米颗粒的大小和表面涂层，以增加对比度并减少肝/脾/巨噬细胞的非特异性摄取。选择5 nm、10 nm、20 nm和30 nm的氧化铁纳米粒子进行尺寸依赖性研究，优化后的氧化铁纳米粒子将被不同量的聚乙二醇包覆以减少对Res的吸收。 3)利用小鼠胰腺癌原位移植瘤模型，研究ATF-氧化铁纳米粒子在肿瘤显像中的特异性和敏感性。我们进行临床前研究，以确定应用ATF？10纳米颗粒在体内检测胰腺癌的最佳成分和条件。

Iron oxide magnetic nanoparticles with high magnetization value and well controlled size and surface chemistry are currently under intense study due to their broad applications in biomedical research. Recent advances in iron oxide synthesis in organic solvents at elevated reaction temperature allows the preparation of size tunable and monodisperse particles. This NIH SBIR project intends to develop this new generation of iron oxide nanoparticles as target specific MRI contrast agents for pancreatic cancer detection. The specific aims are: 1) Prepare iron oxide nanoparticle kits with various surface ligands (such as COOH, NH2, biotin, streptavidin, and IgG) for target specific MR1 imaging. The amount of the functional groups on each nanoparticles will be quantified. 2) Optimize the size and surface coating of the iron oxide nanoparticles for increased contrast and reduced non-specific uptake by liver/spleen/ macrophages. The 5 nm, 10 nm, 20 nm and 30 nm iron oxide nanoparticles will be chosen for the size dependent study, the optimized iron oxide nanoparticles will be coated with the different amount of PEG to reduce RES uptake. 3) Investigate specificity and sensitivity of ATF-iron oxide nanoparticles in tumor imaging using orthotopic mouse pancreatic tumor xenograft models. We conduct preclinical studies to determine the optimal components and conditions for applying ATF¿10 nanoparticles for the detection of pancreatic cancer in vivo.