A bio‐inspired gelatin‐based pH‐ and thermal‐sensitive magnetic hydrogel for in vitro chemo/hyperthermia treatment of breast cancer cells

Abstract Gelatin (Gel)‐based pH‐ and thermal‐responsive magnetic hydrogels (MH‐1 and MH‐2) were designed and developed as novel drug delivery systems (DDSs) for cancer chemo/hyperthermia therapy. For this goal, Gel was functionalized with methacrylic anhydride (GelMA), and then copolymerized with (2‐dimethylaminoethyl) methacrylate (DMAEMA) monomer in the presence of methacrylate‐end capped magnetic nanoparticles (MNPs) as well as triethylene glycol dimethacrylate (TEGDMA; as crosslinker). Afterward, a thiol‐end capped poly( N ‐isopropylacrylamide) (PNIPAAm‐SH) was synthesized through an atom transfer radical polymerization technique, and then attached onto the hydrogel through “thiol‐ene” click grafting. The preliminary performances of developed MHs for chemo/hyperthermia therapy of human breast cancer was investigated through the loading of doxorubicin hydrochloride (Dox) as an anticancer agent followed by cytotoxicity measurement of drug‐loaded DDSs using MTT assay by both chemo‐ and chemo/hyperthermia‐therapies. Owing to porous morphologies of the fabricated magnetic hydrogels according to scanning electron microscopy images and strong physicochemical interactions (e.g., hydrogen bonding) the drug loading capacities of the MH‐1 and MH‐2 were obtained as 72 ± 1.4 and 77 ± 1.8, respectively. The DDSs exhibited acceptable pH‐ and thermal‐triggered drug release behaviors. The MTT assay results revealed that the combination of hyperthermia therapy and chemotherapy has synergic effect on the anticancer activities of the developed DDSs.