Thermoresponsive Magnetic Hydrogels as Theranostic Nanoconstructs

Abstract

We report the development of thermoresponsive magnetic hydrogels based on poly(N-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) T2 (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 (r2) 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.

Biodegradable Self‐Assembled Nanoparticles of Galactose‐Containing Amphiphilic Triblock Copolymers for Targeted Delivery of Paclitaxel to HepG2 Cells

“…It is worth mentioning that such a low CMC endows stability and prolonged circulation time properties to NPs, and guarantees that the NPs reach the target sites before drug release. [47][48][49] …”

Magneto-thermally responsive hydrogels for bladder cancer treatment: Therapeutic efficacy and in vivo biodistribution

“…Magnetic nanostructures were synthesized via high temperature decomposition of iron oleate complex [6,22]. In a typical experiment 10 [23].…”

“…The synthesis of magnetic hydrogels (HG-MNS) was carried out following established [6], [24] protocol. In brief, NIPAAm monomer (40 mM, 361.6 mg, 80 mL water) was mixed with MBAAm (100 mM, 123 mg, 8 mL water) and a 4-neck flask and degassed for ½ hr.…”

“…The imaging and topographical features of nanostructures and hydrogels were studied by using transmission electron microscopy (TEM, Hitachi 8100) and atomic force microscopy (AFM, Veeco Icon). Further the LCST of the nanocomposite sample was determined using DSC (differential scanning calorimetry, Micro-Cal, USA) for change in enthalpy versus temperature following standard protocol [6].…”

“…Intermolecular hydrogen bonding responsible for the hydrophilicity of the material decrease with temperature and eventually, above the lower critical solution temperature (LCST) the material turns hydrophobic. The clinical potential of these hydrogels includes drug delivery [4], [5], cancer theranostics [6], cellular delivery [7], sensors and actuators [8], protein immobilization [9] , [10], microfluidic devices [2], tissue engineering, and regenerative medicine [11], [12] etc. Apart from clinical side, their utility in temperature controlled internalization of ionic molecules in synthetic nanopores was documented as well [13].…”