title: Effect of surface properties of silica nanoparticles on their cytotoxicity and cellular distribution in murine macrophages.
abstract: Surface properties are often hypothesized to be important factors in the development of safer forms of nanomaterials (NMs). However, the results obtained from studying the cellular responses to NMs are often contradictory. Hence, the aim of this study was to investigate the relationship between the surface properties of silica nanoparticles and their cytotoxicity against a murine macrophage cell line (RAW264.7). The surface of the silica nanoparticles was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C). First, the properties of the silica nanoparticles were characterized. RAW264.7 cells were then exposed to nSP70, nSP70-N, or nSP70-C, and any cytotoxic effects were monitored by analyzing DNA synthesis. The results of this study show that nSP70-N and nSP70-C have a smaller effect on DNA synthesis activity by comparison to unmodified nSP70. Analysis of the intracellular localization of the silica nanoparticles revealed that nSP70 had penetrated into the nucleus, whereas nSP70-N and nSP70-C showed no nuclear localization. These results suggest that intracellular localization is a critical factor underlying the cytotoxicity of these silica nanoparticles. Thus, the surface properties of silica nanoparticles play an important role in determining their safety. Our results suggest that optimization of the surface characteristics of silica nanoparticles will contribute to the development of safer forms of NMs.
authors.affiliation: Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. tomoaki@phs.osaka-u.ac.jp.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nabeshi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Arimori
authors.forename: Tokuyuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Saeko
authors.initials: S
authors.lastname: Tochigi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hirai
authors.forename: Takanori
authors.initials: T
authors.lastname: Akase
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Norio
authors.initials: N
authors.lastname: Itoh
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi