The next generation of nanoparticles for biomedical uses will serve multiple functions using a single formulation: for example, magnetic nanoparticles that allow targeted drug delivery and magnetic imaging. One of the primary reasons magnetic targeting has not fulfilled its promise is that the magnetic moment of a nanoparticle decreases with size. Since the magnetic force on the particle is equal to the product of the externally applied magnetic-field gradient and particle's magnetic moment, developing nanoparticles with significantly greater moment is critical. Our overall goal is to develop novel magnetic nanoparticles with high magnetic moments that simultaneously optimize multiple functionalities i.e. effective drug targeting and increased detection sensitivity via magnetic imaging. The specific objectives of these studies are to fabricate magnetic nanoparticles with materials and compositions optimized to produce higher magnetic moments, formulate these nanoparticles into a water- based system that can be loaded with high doses of anticancer agents, functionalize nanoparticles with antibodies, and evaluate these multifunctional nanoparticles for tumor-specific magnetic drug targeting and early detection of tumor using magnetic resonance imaging. The proposed objectives will be achieved with a multidisciplinary collaborative research effort involving pharmaceutics and drug delivery, physics and biomaterial synthesis, and bioimaging technology.
The specific aims of the proposal are:
Aim 1 : To fabricate superparamagnetic nanoparticle fluids and characterize their magnetic and other physical properties;
Aim 2 : To study biocompatibility, test different formulation parameters for drug loading and release, and determine antiproliferative effects of the drug-loaded magnetic nanoparticles in vitro;
Aim 3 : To study biodistribution of magnetic nanoparticles, magnetic targeting in response to an external magnetic field, and demonstrate tumor inhibition in a murine model of breast cancer;
Aim 4 : To determine the MRI detection threshold of magnetic nanoparticles for early detection of tumor. We anticipate that the novel magnetic nanomaterials developed in this proposal will overcome the major issues in magnetic drug targeting as well as achieve a high degree of sensitivity for early detection of tumor. The materials developed also can be used in other disease conditions for therapeutic and diagnostic purposes. These multifunctional magnetic nanoparticles will serve as platforms for these and other biomedical applications. ? ?
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