NANOPARTICLES OF MAGNETIC IRON OXIDES AS PROSPECTIVE DIAGNOSTIC AGENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的目标是获得嵌入在非聚合生物兼容的可变覆盖率的有机外壳中的新型超小氧化铁基磁性颗粒，并测试它们作为癌症和其他疾病诊断的细胞标记和磁共振造影剂的前景。我们假设，与聚合物覆盖的颗粒相比，覆盖在颗粒表面的小分子覆盖配体将为潜在的标记剂提供更大的流动性和扩散。我们还提出了一个假设，即改变有机壳层的分子结构和厚度有助于改变不同磁共振应用所需的质子弛豫机制。所获得的材料可以很好地替代目前使用的有毒的Gd造影剂。我们建议：(A)合成磁铁矿和/或磁铁矿纳米颗粒，其核心尺寸为2-4 nm，并研究其结构和磁性。这将通过在无表面活性剂的均相溶液中对螯合铁(II)和(III)络合物进行高温水解来实现。(B)将合成的纳米晶与不同的羟基羧酸反应，研究纳米晶-配体界面的分子结构对纳米粒子胶体结构和稳定性的影响。(C)优化作为潜在细胞标记和磁共振造影剂的复合粒子的设计。这将通过改变纳米晶体-有机壳层界面的结构和改变晶核与有机壳层尺寸的比例来解决。界面(内球)的结构将通过改变纳米晶体的配体覆盖率和改变配体主链的分子结构来控制。颗粒尺寸将通过改变纳米晶体尺寸和形成纳米颗粒外球的覆盖配体的侧取代基的几何形状来调整。 合成的磁性材料将被提供给生物研究机构以评估其细胞毒性，并提供给放射机构以研究其驰豫特性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to obtain new ultrasmall iron oxide-based magnetic particles embedded in a nonpolymeric biocompatible organic shell with variable coverage and to test them as prospective cell labeling and MRI contrast agents for cancer and other diseases diagnostics. We hypothesize that small-molecule capping ligands covering the particles' surface will provide greater mobility and diffusion for a potential labeling agent when compared to polymer-covered particles. We also have a hypothesis that varying the molecular structure and thickness of the organic shell can help with changing the mechanism of the proton relaxation which is needed for different MRI applications. The obtained materials can be good alternatives to currently used toxic gadolinium contrast agents. We are proposing: (a) To synthesize the nanoparticles of magnetite and/or maghemite, with the core dimensions of 2-4 nm, and to study their structure and magnetic properties. This will be done by high-temperature hydrolysis of chelated iron (II) and (III) complexes in surfactant-free homogeneous solutions. (b) To react the synthesized nanocrystals with various hydroxycarboxylic acids and to study the influence of the molecular structure at the nanocrystal-ligand interface on structure and stability of the nanoparticles' colloids. (c) To optimize the design of the composite particles as potential cell labeling and MRI contrast agents. This will be addressed by changing the structure of the nanocrystal-organic shell interface and by changing the crystal core to organic shell size ratio. The structure of the interface (inner sphere) will be controlled by changing the ligand coverage of the nanocrystals and changing the molecular structure of the ligands' backbone. Particle dimensions will be adjusted by varying the nanocrystal size and the geometry of the capping ligand's side substituent which forms the outer sphere of the nanoparticle. The synthesized magnetic materials will be provided to biological research facilities for evaluation of their cytotoxicity and to radiology facilities to study their relaxivity properties.