title: High-content screening as a universal tool for fingerprinting of cytotoxicity of nanoparticles.
abstract: Recent advances and progress in nanobiotechnology have demonstrated many nanoparticles (NPs) as potential and novel drug delivery vehicles, therapeutic agents, and contrast agents and luminescent biological labels for bioimaging. The emergence of new biomedical applications based on NPs signifies the need to understand, compare, and manage their cytotoxicity. In this study, we demonstrated the use of high-content screening assay (HCA) as a universal tool to probe the cytotoxicity of NPs and specifically cadmium telluride quantum dots (CdTe QDs) and gold NPs (Au NPs) in NG108-15 murine neuroblastoma cells and HepG2 human hepatocellular carcinoma cells. Neural cells represent special interest for NP-induced cytotoxicity because the optical and electrical functionalities of materials necessary for neural imaging and interfacing are matched well with the properties of many NPs. In addition, the cellular morphology of neurons is particularly suitable for automated high content screening. HepG2 cells represent a good model for high content screening studies since they are commonly used as a surrogate for human hepatocytes in pharmaceutical studies. We found the CdTe QDs to induce primarily apoptotic response in a time- and dosage-dependent manner and produce different toxicological profiles and responses in undifferentiated and differentiated neural cells. Au NPs were found to inhibit the proliferation and intracellular calcium release of HepG2 cells.
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Jan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Byrne
authors.forename: Meghan
authors.initials: M
authors.lastname: Cuddihy
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Davies
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
authors.forename: Yurii K
authors.initials: YK
authors.lastname: Gun'ko
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kotov
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay / Q000379:methods*; D002460:Cell Line; D003603:Cytotoxins; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D003603:Cytotoxins