Redox-responsive degradable microgel modified with superparamagnetic nanoparticles exhibiting controlled, hyperthermia-enhanced drug release

Abstract A novel degradable microgel based on poly(N-isopropylacrylamide) (pNIPA) cross-linked with N,N’-bisacryloylcystine (BISS) and containing superparamagnetic iron oxide nanoparticles (SPION@CA) was synthesized by semi-batch precipitation polymerization and examined as a potential hyperthermia-enhanced drug carrier. The pNIPA provided the microgel with temperature sensitivity, the BISS was responsible for degradation in the presence of glutathione (GSH) (an –S–S–bond reductor naturally present in cells), while the SPION@CA permitted remote control of temperature to improve drug release. The microgels exhibited volume phase transition temperature at ca. 34 °C, which is near the human body temperature, and were stable across a wide range of temperatures and ionic strengths, as well as in the blood plasma at 37 °C. It was found that the presence of SPION@CA in the polymer network of the microgels enabled the temperature to be increased up to 42 °C by an alternating magnetic field, and that increasing the temperature from 37 to 42 °C significantly enhanced the releasing of the anticancer drug doxorubicin (DOX). The highest DOX release (82%) was observed at pH 5, 42 °C, and in the presence of GSH, and the lowest (20%) at pH 7.4, 37 °C, and in the absence of GSH. MTT assay indicated that compared to free doxorubicin, the microgel particles loaded with doxorubicin have comparable cytotoxicity against MCF-7 cancer cells while being significantly less toxic to MCF-10A healthy cells. Graphical abstract