In this study, thermoresponsive hydrogel microspheres, namely, poly(N-isopropylacrylamide) (PNIPAAm) were prepared by using an inverse suspension polymerization technique. The radiation-induced modification of PNIPAAm microspheres with itaconic acid (IA) was applied for synthesizing pH and thermoresponsive PNIPAAm-co-poly(itaconic acid) microspheres (PNIPAAm-co-PIA). The PNIPAAM-co-PIA microspheres were simply immersed with iron (Fe2+, Fe3+) ions. In order to investigate drug release behavior of the prepared microspheres, 5-Fluorouracil as a model drug, namely, anti-cancer drug.