Polystyrene coated iron-platinum drug delivery platforms for theranostics
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Cancer is the second leading cause of death in the United States, exceeded only by heart disease, and it is estimated that one in every four deaths is due to cancer.1 Many therapeutic techniques that are currently used are often severely limited and can cause adverse effects, which prevents the aggressive treatment of late stage cancers. Significant improvements are needed involving early detection and more selective treatment options. Much interest has been shown in the development of materials that are highly selective and capable of being used in both therapeutic and diagnostic applications.2,3 nanoparticles have been shown to passively accumulate in tumors, making them useful materials for developments in cancer research.4 Iron-platinum (FePt) nanoparticles have an excellent potential as delivery agents for medicinal applications. Superparamagnetic FePt nanoparticles were embedded in a surface-functionalized polymeric shell as drug delivery platforms. The FePt core offers improved characteristics for magnetic resonance imaging (MRI) over currently used materials. The FePt nanoparticles were optimized to sizes between 2 to 6 nanometers and their physical and magnetic properties were also analyzed. The amount of surfactants used during the synthesis had a significant effect on the size and shape of the nanoparticles. The altered synthetic parameters resulted in the formation of both cubic and spherical nanoparticles. Face-centered cubic (fcc) unit cell structures were produced, which could also be thermally annealed to form the more ordered face-centered tetragonal (fct) structures. The fcc and fct unit cell structures of the FePt nanoparticles were characterized using powder X-ray diffraction (XRD). The FePt nanoparticle cores were coated using an emulsion polymerization reaction to increase their stability in biological systems.5 The polystyrene coating was optimized to produce an overall size of approximately 12 to 30 nanometers. The magnetic characteristics of the coated FePt nanoparticles were analyzed by MRI. Dynamic light scattering (DLS), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), and inductively coupled plasma mass spectrometry (ICP-MS) were also used to characterize the size and composition of the nanoparticles. The coated nanoparticles were functionalized with azides on the surface and analyzed using both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). beta-cyclodextrin was attached to the surface of the nanoparticles using a click chemistry reaction. The hydrophobic cavity of the beta-cyclodextrin allows for the incorporation of hydrophobic drugs for subsequent delivery. These superparamagnetic FePt coated and functionalized nanoparticles show great potential to selectively treat and diagnosis various types of cancer and diseases.6 Furthermore, there are numerous drugs such as FK866, doxorubicin, gemcitabine, and paclitaxel that are used to treat various types of cancer. Many of these drugs have different mechanisms by which they cause cell death. New derivatives of FK866, considered to be one of the most potent anti-cancer drugs, have been developed through the inclusion of carboranes.7,8 These drugs have shown increased potency and antiproliferative activity against cancer cells in vitro through the use of various cell culture assays.9/11 The inhibitory concentrations on various cells lines were reported through the use of MTT colorimetric assays.12 Drug combinations were also performed and analyzed using CompuSyn to determine the existence of any synergistic effects.
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