(286b) 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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