title: The applicability of conventional cytotoxicity assays to predict safety/toxicity of mesoporous silica nanoparticles, silver and gold nanoparticles and multi-walled carbon nanotubes.
abstract: Developing new, validated methods for screening of the effects of nanomaterials is a huge and expensive task. It is therefore necessary to try to employ already existing and validated methods, developed for chemicals. In the present study cytotoxicity of gold (Au) and silver (Ag) nanoparticles (NP), two different mesoporous silica nanoparticles (MSNP), and multi-walled carbon nanotubes (MWCNT) were investigated in BALB/c 3T3 fibroblasts, NR8383 macrophages, and U937 monocytes using standard assays, namely WST-1 and NRU. In addition, preliminary attempts were made to investigate ENM-mediated effects on cell motility as a potential end point for NP toxicity. AgNPs were most toxic to BALB/c 3T3 fibroblasts while other ENMs were insignificantly toxic. NR8383 macrophages were most sensitive cells, as in addition to AgNPs, also MWCNTs were toxic to NR8383 cells. AgNP was toxic also to U937 cells, other ENMs had minor effect. Different media resulted in different-sized aggregates of the same ENMs. AgNP inhibited BALB/c motility most, whereas NR8383 motility was inhibited most by MWCNTs. In conclusion, conventional cytotoxicity assays are better suited to rank the order of toxicity of different nanoparticles instead of producing accurate IC50 data. Moreover, using immune cells, especially macrophages together with fibroblasts, would bring more relevant predictions of ENM cytotoxicity as immune cells may discover cytotoxicity that is not captured by BALB/c 3T3 cells alone.
authors.affiliation: The Finnish Centre for Alternative Methods, School of Medicine, University of Tampere, Tampere, Finland. Electronic address: marika.mannerstrom@uta.fi.
authors.forename: Marika
authors.initials: M
authors.lastname: Mannerström
authors.affiliation: Hearing and Balance Research Unit, Field of Otolaryngology, School of Medicine, University of Tampere, Tampere, Finland; Department of Otolaryngology-Head and Neck Surgery, Center for Otolaryngology-Head & Neck Surgery of Chinese PLA, Shanghai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: The Finnish Centre for Alternative Methods, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Toimela
authors.affiliation: Hearing and Balance Research Unit, Field of Otolaryngology, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
authors.affiliation: The Finnish Centre for Alternative Methods, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Heinonen
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D001681:Biological Assay; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006046:Gold / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D016062:Porosity; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties; D018675:Toxicity Tests; D020298:U937 Cells
chemical_list: D037742:Nanotubes, Carbon; D012834:Silver; D006046:Gold; D012822:Silicon Dioxide
keywords: Cell motility; Cytotoxicity in vitro; Engineered nanomaterials; Fibroblasts; Macrophages; Monocytes