(385d) Synthesis and Characterization of PEG-Iron Oxide Core-Shell Nanoparticles for Dual Hyperthermia and Chemotherapy Treatment of Cancer

Synthesis and
Characterization of PEG-Iron Oxide Core-shell Nanoparticles for Dual
Hyperthermia and Chemotherapy Treatment of Cancer

Robert J. Wydra¹,
Anastasia M. Kruse¹, Younsoo Bae², Kimberly W. Anderson¹,
J. Zach Hilt¹

¹Department
of Chemical and Materials Engineering, University of Kentucky

²Department
of Pharmaceutical Sciences, University of Kentucky

Hyperthermia,
the heating of tissue in the 41-45°C range, can induce cellular death on its
own or work in conjunction with chemotherapy for improved cancer therapy [1]. 
In this study, core-shell nanocomposites were prepared with the intent of
co-delivery of a chemotherapeutic (Geldanamycin and
17-N-Allylamino-17-demethoxygeldanamycin) and heat.  The core-shell
nanoparticles were prepared using atomic transfer radical polymerization (ATRP)
to coat iron oxide (Fe₃O₄) nanoparticles with a
poly(ethylene glycol) (PEG) based  polymer shell.  The iron oxide core allows
for the remote heating of the particles in an alternating magnetic field
(AMF).  Nanoparticle mediated thermal therapy feasibility was demonstrated in
vitro with a thermoablation (55°C) study on A549 lung carcinoma cells. 
Combinational therapy of chemotherapeutic and hyperthermia on A549 was
investigated to demonstrate an enhanced therapeutic effect.

FTIR
measurements verified the PEG coating by observing peaks at 1715cm^-1
and 1105cm^-1, which represent the carbonyl group (C=O) and ether
group (C-O-C), respectively.  TGA indicated different mass loss profiles and
slight differences in overall mass loss between the core citrate coated
particles and the polymer coated particles.   The results from thermal therapy
demonstration indicated that there is no toxic effect from the AMF coil or
particles in solution over the timeframe of the experiment.  When the particles
were exposed to the AMF field, there was complete cellular death as a result of
the heat generate by the nanoparticles.

ATRP was
successfully utilized to coat iron oxide nanoparticles with a PEG based polymer
shell.  For the time frame of the thermal therapy experiments, there is a
minimal toxic effect observed in A549 cells for the 10 mg/ml concentration of
PEG-coated Fe₃O₄ nanoparticles.  Thermoablation of A549
demonstrates the potential use of polymer coated particles for thermal
therapy.  Future work involves the refinement of the dual therapy study to
demonstrate a synergistic effect of a co-delivery of chemotherapeutics and
hyperthermia from magnetic nanoparticles.

References:

[1] Issels RD.
Eur J Cancer. 2008:44:2546-2554.