title: Methotrexate-conjugated and hyperbranched polyglycerol-grafted Fe₃O₄ magnetic nanoparticles for targeted anticancer effects.
abstract: Superparamagnetic nanoparticles grafted with hyperbranched polyglycerol (HPG) and conjugated with methotrexate (MTX) (MNP-g-HPG-MTX) were synthesized via a sol-gel reaction followed by thiol-ene click chemistry and esterification reaction. The successful grafting of MTX and HPG onto the nanoparticles was confirmed by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) spectroscopy, and UV-visible spectroscopy. The HPG-graft layer confers the magnetic nanoparticles with good dispersibility and stability in aqueous medium and macrophage-evasive property while the MTX acts as a chemotherapeutic drug as well as a tumor targeting ligand. The dose-dependent targeting and anticancer effect of the MNP-g-HPG-MTX nanoparticles were evaluated, and the results showed that depending on the amount of conjugated MTX and the concentration of the incubated nanoparticles, the uptake of MNP-g-HPG-MTX nanoparticles by human head and neck cancer (KB) cells can be eight times or more higher than those by 3T3 fibroblasts and RAW macrophages. As a result, the MNP-g-HPG-MTX nanoparticles are capable of killing ∼50% of the KB cells while at the same time exhibiting low cytotoxicity towards 3T3 fibroblasts and RAW macrophages. Thus, such nanoparticles can potentially be used as active targeting anticancer agents.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 117576, Singapore.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Koon-Gee
authors.initials: KG
authors.lastname: Neoh
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Bao-Yu
authors.initials: BY
authors.lastname: Zong
authors.forename: Jia Yong
authors.initials: JY
authors.lastname: Tan
authors.forename: En-Tang
authors.initials: ET
authors.lastname: Kang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004705:Endocytosis / Q000187:drug effects; D005990:Glycerol / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D011108:Polymers; C043941:polyglycerol; D005990:Glycerol; D008727:Methotrexate