Protein adsorption of ultrafine metal oxide and its influence on cytotoxicity toward cultured cells

Masanori Horie, Keiko Nishio, Katsuhide Fujita, Shigehisa Endoh, Arisa Miyauchi, Yoshiro Saito, Hitoshi Iwahashi, Kazuhiro Yamamoto, Hideki Murayama, Hajime Nakano, Naoki Nanashima, Etsuo Niki, Yasukazu Yoshida

Research output: Contribution to journalArticlepeer-review

251 Citations (Scopus)


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, TiO 2, CeO 2, SiO 2, and Fe 2O 3, to Dulbecco's modified Eagle's medium supplemented with a 10% fetal bovine serum (DMEM-FBS) component such as serum proteins and Ca 2+ were estimated. All of the metal oxide nanoparticles adsorbed proteins and Ca 2+ in the DMEM-FBS; in particular, TiO 2, CeO 2, 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 TiO 2 and CeO 2 dispersions. The supernatant showed depletion of serum proteins and Ca 2+ 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 TiO 2. The adsorption ability of TiO 2 depended on the primary particle size. The TiO 2 nanoparticles were size dependently absorbed with proteins and Ca 2+, 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.

Original languageEnglish
Pages (from-to)543-553
Number of pages11
JournalChemical Research in Toxicology
Issue number3
Publication statusPublished - 2009 Mar 16


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