Thermal- and radiation-sensitive hydrogel based on hydroxyethyl cellulose and manganese dioxide nanoparticles for synergistic chemoradiotherapy of breast cancer

Abstract

A thermal- and radiation-sensitive nanocomposite hydrogel-based drug delivery system (DDS) composed of hydroxyethyl cellulose (HEC), poly(N-isopropylacrylamide) (PNIPAAm), and manganese dioxide nanoparticles (MnO2 NPs) was developed for in vitro synergistic chemoradiotherapy of breast cancer cells. For this aim, MnO2 NPs were synthesized in super basic medium, and then their surfaces were modified by a methacrylate-end capped silane coupling agent. The thermal- and radiation-sensitive hydrogel was then synthesized through a free radical copolymerization of HEC, NIPAAm monomer, and modified NPs in the presence of a crosslinker. The lower critical solution temperature (LCST) for the DDS was obtained as 37.5-40°C by de-swelling test at various temperatures. The developed hydrogel was physically loaded with doxorubicin (Dox), and its drug loading capacity and in vitro thermal-triggered drug release behavior were investigated. Anticancer activity of the fabricated DDS/Dox in chemotherapy, radiotherapy, and synergistic chemoradiotherapy were assessed by MTT-assay, and it was found that the dosage of 5 μgmL−1 with applying 2 Gy at 48 hours is the optimum for the synergistic chemoradiotherapy of breast cancer cells. This low concentration of DDS as well as low radiation dose can be lead to proper therapy outcomes with minimum side effects.