Thermoresponsive Magnetic Hydrogels as Theranostic Nanoconstructs

We report the development of thermoresponsive magnetic hydrogels based on poly­(<i>N</i>-isopropylacrylamide) encapsulation of Fe₃O₄ magnetic nanostructures (MNS). In particular, we examined the effects of hydrogels encapsulated with poly-ethylene glycol (PEG) and polyhedral oligomeric silsesquioxane (POSS) surface modified Fe₃O₄ MNS on magnetic resonance (MR) <i>T</i>₂ (transverse spin relaxation) contrast enhancement and associated delivery efficacy of absorbed therapeutic cargo. The microstructural characterization reveal the regular spherical shape and size (∼200 nm) of the hydrogels with elevated hydrophilic to hydrophobic transition temperature (∼40 °C) characterized by LCST (lower critical solution temperature) due to the presence of encapsulated MNS. The hydrogel-MNS (HGMNS) system encapsulated with PEG functionalized Fe₃O₄ of 12 nm size (HGMNS-PEG-12) exhibited relaxivity rate (<i>r</i>₂) of 173 mM^–1s^–1 compared to 129 mM^–1s^–1 obtained for hydrogel-MNS system encapsulated with POSS functionalized Fe₃O₄ (HGMNS-POSS-12) of the same size. Further studies with HGMNS-PEG-12 with absorbed drug doxorubicin (DOX) reveals approximately two-fold enhance in release during 1 h RF (radio-frequency) field exposure followed by 24 h incubation at 37 °C. Quantitatively, it is 2.1 μg mg^–1 (DOX/HGMNS) DOX release with RF exposure while only 0.9 μg mg^–1 release without RF exposure for the same period of incubation. Such enhanced release of therapeutic cargo is attributed to micro-environmental heating in the surroundings of MNS as well as magneto-mechanical vibrations under high frequency RF inside hydrogels. Similarly, RF-induced in vitro localized drug delivery studies with HeLa cell lines for HGMNS-PEG-12 resulted in more than 80% cell death with RF field exposures for 1 h. We therefore believe that magnetic hydrogel system has in vivo theranostic potential given high MR contrast enhancement from encapsulated MNS and RF-induced localized therapeutic delivery in one nanoconstruct