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A bio-inspired gelatin-based pH- and thermal-sensitive magnetic hydrogel for in vitro chemo/hyperthermia treatment of breast cancer cells
Authors:Hossein Derakhshankhah  Rana Jahanban-Esfahlan  Somayeh Vandghanooni  Sattar Akbari-Nakhjavani  Bakhshali Massoumi  Babak Haghshenas  Aram Rezaei  Amir Farnudiyan-Habibi  Hadi Samadian  Mehdi Jaymand
Affiliation:1. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran;2. Department of Medical Biotechnology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;3. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;4. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Chemistry, Payame Noor University, Tehran, Iran;6. Regenerative Medicine Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran;7. Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran;8. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

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.
Keywords:bioengineering  biomaterials  biomedical applications  drug delivery systems
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