282717 Internalization Pattern of Functionalized Magnetic Nanoparticles and the Prospects of Intracellular Hyperthermia
Internalization pattern of functionalized magnetic nanoparticles and the prospects of intracellular hyperthermia
Robert J. Wydra1, Younsoo Bae2, Kimberly W. Anderson1, J. Zach Hilt1
1Department of Chemical and Materials Engineering, University of Kentucky
2Department of Pharmaceutical Sciences, University of Kentucky
Magnetic nanoparticles are being studied for a wide range of biomedical applications such as imaging, targeted delivery, and thermal therapy of cancer. In most cases, the nanoparticles rely on passive targeting to systemically circulate and accumulate in tumors via the phenomenon known as the enhanced permeation and retention effect. To increase specific interactions with cells, nanoparticles can be functionalized with appropriate ligands. It has recently been demonstrated by Rinaldi and others that internalized nanoparticles can induce cellular death when exposed to an alternating magnetic field without a measurable temperature rise. In this study, four nanoparticle systems – uncoated iron oxide, citric acid coated iron oxide, (3-aminopropyl)trimethoxysilane (APTMS), and poly(ethylene glycol) (PEG) coated iron oxide – were incubated with cancer cells and assessed for their ability to be internalized and to be used for intracellular hyperthermia. The iron oxide core nanoparticles, which are selected for their ability to remotely actuate in an AMF, were prepared utilizing the facile co-precipitation technique. The citric acid stabilizer was added in a one-step method and provided a negative surface charge in physiological conditions. APTMS was attached to the particle surface through a ligand exchange and provided a posited charged surface. The PEG coating was selected to increase circulation time and avoid reticuloendothelial system clearance. This coating was prepared with a surface initiated polymerization, atom transfer radical polymerization, where-by an initiator is initially attached to the particle surface and the polymerization extends from the surface. The particles were characterized using Fourier transform infrared spectroscopy to verify surface functionalization; thermal gravimetric analysis to quantify mass percent of coating; dynamic light scattering to determine particle size; and UV-Vis spectroscopy to determine particle stability in a variety of media. Nanoparticles were incubated with A549 lung adenocarcinoma cells and PC3 prostate cancer cells and the internalization pattern was determined by visualization using fluorescent microscopy. Nanoparticle uptake by cancer cells was quantified with the 1,10-phenanthroline colorimetric assay. Cells with internalized nanoparticles were exposed to an AMF to determine the potential for intracellular hyperthermia.
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