MTX-Loaded Dual Thermoresponsive and pH-Responsive Magnetic Hydrogel Nanocomposite Particles for Combined Controlled Drug Delivery and Hyperthermia Therapy of Cancer.

In recent years, the exploitation of magnetic nanoparticles in smart polymeric matrices have received increased attention in several fields as site-specific drug delivery systems. Here, ultrasonic-assisted emulsion copolymerization of N-isopropylacrylamide (NIPAM) and 2-(N,N-diethylaminoethyl) methacrylate (DEAEMA) in the presence of Fe3O4 nanoparticles was employed to prepare pH- and temperature-responsive magnetite nanocomposite particles (MNCPs). The obtained MNCPs were fully characterized by TEM, DSC, FT-IR, VSM, and XRD techniques. They had an average particle size of 70 nm with a lower critical solution temperature of 42 °C and superparamagnetic properties. In addition, MNCPs were loaded with methotrexate (MTX) as an anticancer drug, and their in vitro drug release was studied in different pH values and temperatures and in the presence of an alternating magnetic field. Noteworthy that the highest rate of MTX release was observed at pH 5.5 and 42 °C. Cell viability of the treated MCF-7 human breast cancer cell line with free MTX, MNCPs, and MTX-loaded MNCPs or in combination with magnetic hyperthermia (MHT) and water-based hyperthermia was comparatively studied. The obtained results showed about 17% higher antiproliferative activity for the MTX-loaded MNCPs accompanied by MHT relative to that of free MTX.