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“Design of Poly(ethylene glycol)-Polycaprolactone Diblock Micelles with RGD Targeting Ligands and Embedded Iron Oxide Nanoparticles for Thermally-activated Release”

Published online by Cambridge University Press:  07 March 2012

Christopher S. Brazel
Affiliation:
Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL 35487 USA
James B. Bennett
Affiliation:
Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL 35487 USA
Amanda L. Glover
Affiliation:
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487 USA
Jacqueline A. Nikles
Affiliation:
Department of Chemistry, The University of Alabama at Birmingham, Birmingham, AL 35294
Maaike Everts
Affiliation:
Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35294
Joel N. Glasgow
Affiliation:
Department of Microbiology, The University of Ala. at Birmingham, Birmingham, AL 35294
David E. Nikles
Affiliation:
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487 USA
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Abstract

A thermally-activated micelle consisting of a crystallizable poly(caprolactone), PCL, core and a poly(ethylene glycol), PEG, corona was developed to contain magnetic nanoparticles and anti-cancer agent doxorubicin as well as display a targeting RGD peptide. This system has the potential to target cancer cells, deliver combination hyperthermia and chemotherapy, and offer magnetic resonance imaging contrast. The micelles self-assemble in aqueous solutions and form a crystalline core with a melting transition ranging from 40 to 50 °C, depending on the length of the PCL blocks, with dynamic light scattering showing micelle sizes typically ranging from 20 to 100 nm, depending on block lengths and added drug or nanoparticles. The micelles become unstable as they are heated above their melting point, creating a thermally-activated drug release mechanism. By adding magnetite (Fe3O4) nanoparticles into the PCL core, the micelles can be heated using an externally applied AC magnetic field to induce hyperthermia in combination with the thermally-activated drug release. The polymers and magnetic nanoparticles (MNPs) were synthesized and characterized in our laboratories. The melting transitions of the PCL micelle cores were investigated using microcalorimetry. The heating of nanoparticles and magnetomicelles was conducted using a custom-built hyperthermia coil capable of generating fields of several hundred Oersteds at frequencies ranging from 50 to 450 kHz. Heating of MNPs was maximized at high field intensities. RGD peptides were attached to the PEG corona using maleimide chemistry, and the ability of the RGD-derivatized micelles to target integrin-expressing cells was investigated using fluorescent dye PKH26 to identify the localization of micelles in cultured human kidney (293) cells in vitro. The crystallizable (and meltable) cores in these micelles were designed to overcome drug leakage common in liposome systems and release the drug on demand after a period of time for localization to integrin receptors.

Type
Research Article
Copyright
Copyright © Materials Research Society 2012

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“Design of Poly(ethylene glycol)-Polycaprolactone Diblock Micelles with RGD Targeting Ligands and Embedded Iron Oxide Nanoparticles for Thermally-activated Release”
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