Folate-conjugated thermal- and pH-responsive magnetic hydrogel as a drug delivery nano-system for “smart” chemo/hyperthermia therapy of solid tumors

Abstract

A folate-conjugated pH- and thermal-sensitive magnetic hydrogel composed of poly(vinyl alcohol) (PVA), poly(N-isopropylacrylamide) (PNIPAAm), folate-conjugated poly(acrylic acid) (PAA-FA), and Fe3O4 nanoparticles (NPs) was developed as a “smart” drug delivery system (DDS) for chemo/hyperthermia therapy of cancer cells. Following fabrication, the hydrogels were incorporated with doxorubicin hydrochloride (Dox) physically. Owing to the porous structure of the polymeric matrix and strong physical interactions between the hydrogel and Dox, the developed DDS showed suitable loading (LE) and encapsulation (EE) efficiencies (7.3 ± 0.26 and 87 ± 2.6%, respectively). At pH 7.4 and 37 °C (physiological condition), low rate of drug release was observed from the DDS. At the tumor condition (lower pH and higher temperature), the DDS presented adequate pH- and thermal-responsive drug release behavior. Cytotoxicity of the Dox-loaded DDS in chemotherapy and hyperthermia/chemotherapy against MCF-7 cells was evaluated by MTT assay. The developed DDS showed synergic cancer therapy process by combination of chemotherapy and hyperthermia approaches.