The long-term goal of this project is to develop novel biocompatible magnetic nanocrystalline materials with suitable properties for use in medicine. Potential applications include their use as magnetic targeted drug carriers for treatment of lethal diseases and as diagnostic tools in magnetic labeling or magnetic resonance imaging. A major limitation to the use of currently available materials in biomedical applications is the lack of well-defined and well-characterized particles that are chemically stable in biological fluids, have large magnetic susceptibility, and low inter-particle interactions. Fulfillment of these tasks simultaneously represents a significant research challenge. This project focuses on the development of better-defined and better-characterized nanoscale particles of magnetic materials (e.g. Fe, Co, their oxides and metal/oxide composites) that would be non-toxic and stable in human fluids at physiological pH. Our strategy is to design a nanoscale inorganic/organic composite, where the inorganic core alone determines its magnetic properties, while the hydrophilic organic shell controls its stability and solubility in water. As required by a particular application, particles of different sizes and magnetic behavior will be prepared and characterized by transmission electron microscopy, X-ray diffractometry and magnetic measurements. The technique we will use to achieve our goal is uniquely controllable: the formation and growth of the magnetic core and its subsequent encapsulation into a hydrophilic organic shell can be done as separate steps. Newly developed long-chain polydentate hydrophilic bridging ligands will be synthesized and tested for their ability to solubilize and stabilize the nanoparticles in the biological fluids. The ligands will be based on biocompatible compounds and consist of three structural parts: a polydentate donor head prealigned for binding to several metal centers on a nanoparticle surface (e.g. malic, citric or phthalic acids), a long hydrophilic chain (e.g. polyethylene oxide) to assure sufficient separation between the nanoparticle cores, and a terminal functional group for binding biological and/or drug molecules (e.g. COOH, NH2). Solubility, stability and dynamic behavior of the obtained inorganic/organic composite nanoparticles in aqueous solution at physiological pH values will be studied by dynamic optical scattering techniques and spectrophotometry. Based on the results, they will be controlled by varying the length of the substituents and by introducing neutral (CH2OH) and ionic (SO3-) groups along with carboxy and amino termini.
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