title: The protein corona protects against size- and dose-dependent toxicity of amorphous silica nanoparticles.
abstract: Besides the lung and skin, the gastrointestinal (GI) tract is one of the main targets for accidental exposure or biomedical applications of nanoparticles (NP). Biological responses to NP, including nanotoxicology, are caused by the interaction of the NP with cellular membranes and/or cellular entry. Here, the physico-chemical characteristics of NP are widely discussed as critical determinants, albeit the exact mechanisms remain to be resolved. Moreover, proteins associate with NP in physiological fluids, forming the protein corona potentially transforming the biological identity of the particle and thus, adding an additional level of complexity for the bio-nano responses. Here, we employed amorphous silica nanoparticles (ASP) and epithelial GI tract Caco-2 cells as a model to study the biological impact of particle size as well as of the protein corona. Caco-2 or mucus-producing HT-29 cells were exposed to thoroughly characterized, negatively charged ASP of different size in the absence or presence of proteins. Comprehensive experimental approaches, such as quantifying cellular metabolic activity, microscopic observation of cell morphology, and high-throughput cell analysis revealed a dose- and time-dependent toxicity primarily upon exposure with ASP30 (Ø = 30 nm). Albeit smaller (ASP20, Ø = 20 nm) or larger particles (ASP100; Ø = 100 nm) showed a similar zeta potential, they both displayed only low toxicity. Importantly, the adverse effects triggered by ASP30/ASP30L were significantly ameliorated upon formation of the protein corona, which we found was efficiently established on all ASP studied. As a potential explanation, corona formation reduced ASP30 cellular uptake, which was however not significantly affected by ASP surface charge in our model. Collectively, our study uncovers an impact of ASP size as well as of the protein corona on cellular toxicity, which might be relevant for processes at the nano-bio interface in general.
authors.affiliation: Molecular and Cellular Oncology, ENT/University Medical Center Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
authors.forename: Dominic
authors.initials: D
authors.lastname: Docter
authors.affiliation: Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129 Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bantz
authors.affiliation: Molecular and Cellular Oncology, ENT/University Medical Center Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Westmeier
authors.affiliation: Institute of Biochemistry, Westfälische Wilhelms-University, Wilhelm Klemm-Str. 2, 48149 Münster, Germany.
authors.forename: Hajo J
authors.initials: HJ
authors.lastname: Galla
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123 China.
authors.forename: Qiangbin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Pathology, University Medical Centre, Institute of Pathology, Langenbeckstr. 1, 55101 Mainz, Germany.
authors.forename: James C
authors.initials: JC
authors.lastname: Kirkpatrick
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nielsen
authors.affiliation: Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129 Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Maskos
authors.affiliation: Molecular and Cellular Oncology, ENT/University Medical Center Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stauber
keywords: biobarrier; gastrointestinal tract; high-throughput profiling; nanomedicine; nanotoxicity