Development of a pH-sensitive magnetic hydrogel based on chitosan for synergistic chemo/hyperthermia treatment of MCF-7 breast cancer cells.

A pH-responsive magnetic hydrogel was created based on chitosan (CS) for synergistic chemo/hyperthermia therapy of MCF-7 breast cancer cells. For this goal, a mixture of carboxymethylated chitosan (CS-COOH), vinyl acetate monomer (VAc), and methacrylate end-capped magnetic nanoparticles (Fe3O4 NPs) was copolymerized in the presence of a crosslinker to produce a CS-cl-PVAc/Fe3O4 nanocomposite. Drug delivery system (DDS) was obtained after hydrolysis of acetate groups in PVAc segments to hydroxyl groups, in order to covert PVAc to poly(vinyl alcohol) (PVA). The developed DDS showed acceptable saturation magnetization value (8.82 emug- 1), swelling ratio (2730 ± 78%), degradation rate (59 ± 7.5 wt%), protein adsorption capacity (0.192 ± 0.03µgmg), and low hemolysis rate (4.78 ± 0.08%). Doxorubicin (Dox) loading (LE) and entrapment efficiencies for the developed CS-cl-PVA/Fe3O4 nanocomposite hydrogel were quantified as 2.13 and 64.5%, respectively. The DDS showed pH-responsiveness drug release behavior. It was established that the formulated drug has higher release value (80.1%) at cancerous condition (pH 5.5) than the physiological condition (38.7%). The cytocompatibility of the created DDS was approved via MTT-assay on HSF-PI-16 fibroblast cells. Synergistic chemo/hyperthermia therapy with Dox-loaded system showed higher anticancer performance (IC50 = ~ 25 µgmL- 1) than those of the chemotherapy alone (IC50 = ~ 32 µgmL- 1).