title: Synthesis and in vitro evaluation of pH-sensitive magnetic nanocomposites as methotrexate delivery system for targeted cancer therapy.
abstract: This study focuses on the synthesis and in vitro evaluation of magnetic nanocomposites (Fe3O4@LDH) as methotrexate (MTX) delivery system for targeted anticancer therapy. In which, the Fe3O4nanoparticles acted as magnetically responsive carriers; the coating layer of layered double hydroxide (LDH) was used as a storehouse for MTX. The prepared Fe3O4@LDH nanocomposites exhibited a suitable size, good stability and magnetic responsibility (Ms36.66emu/g); MTX successfully intercalated into the LDH of Fe3O4@LDH at an entrapment rate (%) of 91.78% (the drug loading was 18.36%) by host-guest exchange process. Moreover, the release studies in vitro showed that the drug delivery system (Fe3O4@LDH-MTX) had excellent pH-sensitivity, 84.94% of MTX was released within 48h at pH3.5 via the co-effect of dissolution of LDH layer and ion-exchange. WST-1 assays in cancer cells (MCF-7 and HepG2) and normal cells (HUVEC) demonstrated that Fe3O4@LDH-MTX exhibited high anticancer activity while low toxicity to normal cells, and also the Fe3O4@LDH composites were practically non-toxic. Thus, our results revealed that Fe3O4@LDH-MTX would be a competitive candidate for targeted delivery and sustained and controlled release of MTX.
authors.affiliation: National Special Superfine Powder Engineering Research Center, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Aipeng
authors.initials: A
authors.lastname: Deng
authors.affiliation: National Special Superfine Powder Engineering Research Center, Nanjing University of Science and Technology, Nanjing 210094, China. Electronic address: superfine_jw@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: National Special Superfine Powder Engineering Research Center, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Renbing
authors.initials: R
authors.lastname: Tian
authors.affiliation: National Special Superfine Powder Engineering Research Center, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Yewen
authors.initials: Y
authors.lastname: Shen
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008727:Methotrexate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D053761:Nanocomposites / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D008727:Methotrexate
keywords: Controlled release; Fe(3)O(4); LDH; MTX; Targeted therapy; pH-sensitivity