The performance of magnetic nanoparticles as drug delivery, hyperthermia and cell tracking agents depends on their magnetic susceptibility, mobility, and diffusion properties in biological media. Most of the functional nanoparticles on the market today utilize biocompatible polymers which wrap these particles and therefore stabilize their colloids. Since polymers attach to the particle surface randomly, they must be large in order to provide a sufficient stabilizing effect. As a consequence, their diamagnetic contribution to the core-shell nanocomposite obscures its desired response to an external magnetic field. In addition, polymeric shells make the nanocomposite large and thus limit its mobility and penetration properties. The proposed project addresses this problem. The ultimate goal of this project is to develop new synthetic methods for the preparation of non-polymeric- ligand-capped inorganic nanoparticles with superior properties for biomedical applications. The following plan is being proposed to achieve this goal. We will first study the coordination of polydentate 1-hydroxycarboxylic acids to the surfaces of metal oxide nanocrystals in order to gain an understanding of how the structure of the inorganic - organic interface affects the colloidal properties of the nanoparticles. We will use acids whose molecular geometry will likely promote their coordination in a bridging mode, while leaving one or more active groups unbound. Then in order to cover the nanoparticles with a protective layer of a biocompatible organic shell, we plan to perform organic synthesis directly on the surface of the acid-capped nanoparticles using the acid's unbound functional groups. Colloidal alumina will be used along with superparamagnetic iron oxides for the development of organic ligand synthesis which will decrease the possibility of undesired oxidation and also allow the use of NMR for the product analysis. The hypothesis is that organic synthesis techniques developed for alumina will work for iron oxides as well. Alternatively, the alumina-organic nanocomposites will be decomposed using a strong acid or base, and the isolated free ligands will be reacted with the ligand-free iron oxide nanoparticles to assemble the magnetic inorganic core-organic shell nanocomposites. A systematic study of the colloidal stability in aqueous solutions and the magnetic susceptibility measurements will be conducted for the assembled nanocomposites. Dynamic Light Scattering and electrophoretic methods will be used for measuring the hydrodynamic sizes and zeta potentials. The nanocomposites forming the most stable colloids and having the strongest magnetic response will be sent for in vitro testing.
The project aims at the development of novel magnetic delivery agents with superior properties for the targeted treatment of cancer-affected tissues. To assure stability and compatibility with biological fluids, the surface of these polymer-free carriers will be chemically modified by organic synthesis directly on the nanoparticle's surface. This organic synthesis will be developed in the project.
| Nilov, Denis; Kucheryavy, Pavel; Walker, Verina et al. (2014) Synthesis of 5-Substituted Derivatives of Isophthalic Acid as Non-Polymeric Amphiphilic Coating for Metal Oxide Nanoparticles. Tetrahedron Lett 55:5078-5081 |
| Devalapally, Harikrishna; Silchenko, Svitlana; Zhou, Feng et al. (2013) Evaluation of a nanoemulsion formulation strategy for oral bioavailability enhancement of danazol in rats and dogs. J Pharm Sci 102:3808-15 |
| Kucheryavy, Pavel; He, Jibao; John, Vijay T et al. (2013) Superparamagnetic iron oxide nanoparticles with variable size and an iron oxidation state as prospective imaging agents. Langmuir 29:710-6 |
| Vasylenko, Inna V; Gavrylenko, Konstiantyn S; Il'yin, Vladimir G et al. (2010) The metamorphosis of heterometallic trinuclear antiferromagnetic complexes into nano-sized superparamagnetic spinels. Mater Chem Phys 121:47-52 |
