title: Protein adsorption of ultrafine metal oxide and its influence on cytotoxicity toward cultured cells.
abstract: Many investigations about the cellular response by metal oxide nanoparticles in vitro have been reported. However, the influence of the adsorption ability of metal oxide nanoparticles toward cells is unknown. The aim of this study is to understand the influence of adsorption by metal oxide nanoparticles on the cell viability in vitro. The adsorption abilities of six kinds of metal oxide nanoparticles, namely, NiO, ZnO, TiO2, CeO2, SiO2, and Fe2O3, to Dulbecco's modified Eagle's medium supplemented with a 10% fetal bovine serum (DMEM-FBS) component such as serum proteins and Ca2) were estimated. All of the metal oxide nanoparticles adsorbed proteins and Ca2+ in the DMEM-FBS; in particular, TiO2, CeO2, and ZnO showed strong adsorption abilities. Furthermore, the influence of the depletion of medium components by adsorption to metal oxide nanoparticles on cell viability and proliferation was examined. The particles were removed from the dispersion by centrifugation, and the supernatant was applied to the cells. Both the cell viability and the proliferation of human keratinocyte HaCaT cells and human lung carcinoma A549 cells were affected by the supernatant. In particular, cell proliferation was strongly inhibited by the supernatant of TiO2 and CeO2 dispersions. The supernatant showed depletion of serum proteins and Ca2+ by adsorption to metal oxide nanoparticles. When the adsorption effect was blocked by the pretreatment of particles with FBS, the inhibitory effect was lost. However, in NiO and ZnO, which showed ion release, a decrease of inhibitory effect by pretreatment was not shown. Furthermore, the association of the primary particle size and adsorption ability was examined in TiO2. The adsorption ability of TiO2 depended on the primary particle size. The TiO2 nanoparticles were size dependently absorbed with proteins and Ca2+, thereby inducing cytotoxicity. In conclusion, the adsorption ability of metal oxide nanoparticles is an important factor for the estimation of cytotoxicity in vitro for low-toxicity materials.
authors.affiliation: Health Technology Research Center (HTRC), National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31, Midorigaoka, Ikeda, Osaka 563-8577, Japan. masa-horie@aist.go.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Horie
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishio
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Fujita
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Endoh
authors.forename: Arisa
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Murayama
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakano
authors.forename: Naoki
authors.initials: N
authors.lastname: Nanashima
authors.forename: Etsuo
authors.initials: E
authors.lastname: Niki
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002563:Cerium / Q000633:toxicity; D005290:Ferric Compounds / Q000633:toxicity; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012822:Silicon Dioxide / Q000633:toxicity; D014025:Titanium / Q000633:toxicity; D015034:Zinc Oxide / Q000633:toxicity
chemical_list: D005290:Ferric Compounds; D012709:Serum Albumin; C009495:titanium dioxide; C000499:ferric oxide; D012710:Serum Albumin, Bovine; D002563:Cerium; C030583:ceric oxide; D012822:Silicon Dioxide; D009532:Nickel; C028007:nickel monoxide; D014025:Titanium; D015034:Zinc Oxide