(346b) Temperature and Magnetic Field-Responsive Nanoparticles Based On a Superparamagnetic Magnetite Core and a Poly(N-isopropylacrylamide) Shell

Multistimuli-responsive nanostructures have interesting existing and potential in vivo applications. We report on the temperature-induced aggregation and relaxometric behavior of magnetic nanostructures comprised of a magnetite core and a poly(N-isopropylacrylamide) (PNIPAM) shell. Discrete magnetite nanoparticles were synthesized by a high-temperature decomposition method using Iron (III) acetylacetonate as the precursor. Controlled synthesis of bis(phosphonate)-terminated PNIPAM was achieved by atom transfer radical polymerization. Ligand exchange between a dispersion of oleic acid-coated magnetite nanoparticles and the PNIPAM solution afforded highly water-dispersible magnetite-PNIPAM nanoparticles (D_I = 38 nm) with good colloidal stability in physiological media. The hydrodynamic sizes of the core-shell nanoparticles were predicted with a density distribution model using the measured sizes of the magnetite cores (~ 7.8 nm) from transmission electron microscopy. Good agreement between the measured and predicted hydrodynamic sizes suggested that the complexes were primarily discrete, non-agglomerated nanoparticles under ambient conditions. SQuID magnetometry confirmed that the nanoparticles were fully superparamagnetic at 300 K with a saturation magnetization of ~ 55 emu g^-1.   

The PNIPAM shell around the magnetite core afforded thermosensitive properties to the nanoparticles. When heated above ~ 33.5 °C, the intensity-weighted diameter increased rapidly, signaling aggregation induced by the lower critical solution temperature (LCST) of PNIPAM. At the transition temperature, the PNIPAM steric chains lose their water of hydration to become mutually attractive and drive aggregation of the magnetite nanoparticles. Steady-state fluorescence experiments on Nile red-labelled magnetite-PNIPAM nanoparticles at 25 °C (< LCST) and 35 °C (> LCST) showed fluorescence quenching above the LCST because of the aggregation of nanoparticles and concomitant dye aggregation. NMR relaxometry performed on aqueous dispersions of the magnetite-PNIPAM nanoparticles revealed dramatic shortening of transverse relaxation times (T₂) of the water protons and an increase in the relaxometric ratio (R₂/R₁) above the LCST transition of PNIPAM. We envisage that temperature and magnetic field sensitivity offer potential for the design of ‘smart’ multifunctional magnetic nanocarriers for biomedical applications such as site-specific drug delivery and magnetic resonance imaging.