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Kolesnichenko Project
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Nanoparticles of Magnetic Iron Oxides as Prospective Diagnostic Agents

Principal Investigator: Vladimir Kolesnichenko, Ph.D., Assistant Professor, Department of Chemistry

Abstract

The goal of this project is to obtain new ultrasmall iron oxide-based magnetic particles embedded in a non-polymeric 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 might 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 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) diethylene glycol alkoxide complexes in non-aqueous 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.

Specific Aims

The goal of this project is to obtain new iron oxide-based ultra-small magnetic particles embedded in a non-polymeric 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 smaller particles will potentially be better inner-sphere contrast agents, and that they will have greater mobility and diffusion properties through biological boundaries. We also have a hypothesis 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 expect that varying the molecular structure and thickness of the organic shell will affect the rate of water exchange at and near the particle surface, and can help with changing the mechanism of the proton relaxation from inner- or second-sphere to outer-sphere type which is needed for different MRI applications. The obtained materials are expected to be superior to currently used gadolinium contrast agents by several parameters: lower toxicity, adjustable diffusion through biological boundaries and a higher contrasting efficiency. These advantages will facilitate the detection of the malicious tissues, what is critical for early cancer diagnostics.

Specifically we are proposing:

  1. To synthesize surfactant-free nanoparticles of magnetite and/or maghemite, with the dimensions of 2-4 nm, and to study their structural and magnetic properties. Surface of these particles will be temporarily passivated with the adsorbed solvent which is easily substituted with the desired capping ligand.
  2. To study colloid formation of the synthesized ultra-small nanocrystals and their surface reactivity with multifunctional organic compounds. We plan to study the influence of the molecular structure at the nanocrystal-ligand interface on structure and stability of the nanoparticles' colloids. This knowledge will be used as a ground for the synthesis of targeted nanoparticles composed of inorganic nanocrystals coated with small-molecule capping ligands. Studying the structure and properties of the obtained compounds will be done at the facilities of the Major Instrumentation core of the RCMI Center .
  3. To optimize the design of the composite particles as potential cell labeling and MRI contrast agents. Structure of the capping ligand and its size will be used as variables for tuning the relaxivity and diffusion properties, along with coverage of the nanoparticles. Cytotoxicity of the obtained materials will be tested in the Cell and Molecular Biology core of the RCMI Center .
  4. To launch the longer-term studies on specific biorecognition of the contrast agents, and involving more extensive collaboration with biomedical specialists, and to develop a R01-type proposal, based on the obtained results and experience.

Summary of Progress

Aspiring to design and synthesize novel magnetic metal oxide clusters, the research students in Dr. Kolesnichenko's lab studied the condensation of aqueous transition metal ions at a presence of complexing agent in conditions of progressively increasing pH. Tartrate ion was used as a complexing agent, which is capable of acting as a polydentate chelating and bridging ligand. It was determined that tartrate inhibits metal ion condensation due to its chelating effect. Therefore it can be used as a component of reaction solutions that would help controlling kinetics and mechanism of metal ion condensation and crystal growth. Controlling colloid and surface chemistry of the nanocrystals in solution, it can effectively arrest their agglomeration, what opens the possibilities for preparation of the inorganic/organic composite nanoparticulate imaging agents.

Publications:

  1. The metamorphosis of heterometallic trinuclear antiferromagnetic complexes
    into nano-sized superparamagnetic spinels. V. Vasylenko, K. S. Gavrylenko, V. G. Il’yin, V. Golub, G. Goloverda, V. Kolesnichenko, A. W. Addison, V. V. Pavlishchuk, Materials Chemistry and Physics, 2010, 121, 1-2, 47-52.

Presentations:

  1. V. Kolesnichenko, G. Goloverda, S. Sitaula, B. Allison, C. Ezenwoye, R. Fleming,
    E. Powell, V. Walker, and C. Williams. “Synthesis, Colloid and Surface Chemistry of
    Metal Oxide Nanoparticles”, 8-th International Conference “Scientific and Clinical
    Applications of Magnetic Carriers”, Warnemünde, Germany, May 25-29, 2010.
  2. V. Kolesnichenko. “Synthesis, colloid and surface chemistry of magnetic metal and
    metal oxide nanoparticles”, invited talk at the Institute of General and Inorganic Chemistry (Kiev, Ukraine), June 17, 2010.
  3. V. Kolesnichenko, “Synthesis and properties of magnetic metal and metal oxide
    nanoparticles”, invited talk at the Institute of Magnetism (Kiev, Ukraine), June 14, 2010.
  4. V. Kolesnichenko. “Synthesis of magnetic metal and metal oxide nanoparticles with
    controlled surface chemistry”, invited talk at the National Taras Shevchenko University (Kiev, Ukraine), June 3, 2010.
 
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