This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.
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