NANOPARTICLES OF MAGNETIC IRON OXIDES AS PROSPECTIVE DIAGNOSTIC AGENTS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的目标是获得新的超小氧化铁基磁性颗粒，嵌入非聚合物生物相容性有机壳中，覆盖范围可变，并将其作为前瞻性细胞标记和MRI造影剂用于癌症和其他疾病诊断。我们假设，与聚合物覆盖的颗粒相比，覆盖颗粒表面的小分子封端配体将为潜在的标记剂提供更大的流动性和扩散。我们还有一个假设，即改变有机壳的分子结构和厚度可以帮助改变不同MRI应用所需的质子弛豫机制。所获得的材料可以是目前使用的有毒钆造影剂的良好替代品。我们建议：（a）合成核尺寸为2-4 nm的磁铁矿和/或磁赤铁矿纳米颗粒，并研究其结构和磁性能。这将通过螯合铁（II）和（III）络合物在无表面活性剂的均匀溶液中的高温水解来完成。(b)将合成的纳米晶体与不同的羟基羧酸反应，研究纳米晶体-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MRI造影剂的复合颗粒的设计。这将通过改变纳米晶体-有机壳界面的结构和通过改变晶体核与有机壳的尺寸比来解决。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骨架的分子结构来控制。将通过改变形成纳米颗粒的外球的封端配体的侧取代基的尺寸和几何形状来调节颗粒尺寸。 合成的磁性材料将提供给生物研究机构，用于评估其细胞毒性，并提供给放射学机构，用于研究其弛豫特性。

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.