Redox-Responsive Degradable Microgel Modified with Superparamagnetic Nanoparticles Exhibiting Controlled, Hyperthermia-Enhanced Drug Release

A novel degradable microgel based on poly(N-isopropylacrylamide) (pNIPA) cross-linked with N,N’-bisacryloylcystine (BISS) and containing superparam- agnetic iron oxide nanoparticles (SPION@CA) was synthesized by semi-batch precipitation polymerization and examined as a potential hyperthermia-en-hanced drug carrier. The pNIPA provided the microgel with temperature sen-sitivity, 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 signifi- cantly less toxic to MCF-10A healthy cells.