title: Toxicity evaluation of engineered nanoparticles for medical applications using pulmonary epithelial cells.
abstract: There are a multitude of nanoparticles (NPs) which have shown great potentials for medical applications. A few of them are already used for lung therapeutic and diagnostic purposes. However, there are few toxicological studies which determine possible adverse pulmonary responses. It is thus important to propose in vitro screening strategies to evaluate the pulmonary toxicity of NPs used in nanomedicine. Our goal was to determine the cellular effects of several biomedical NPs with different physico-chemical characteristics (chemical nature, size and coating) to establish suitable tests and useful benchmark NPs. The effects of poly(lactic-co-glycolic acid) (PLGA), silica, iron oxide and titanium dioxide NPs were studied using human bronchial (16HBE) and alveolar epithelial cells (A549). We evaluated cytotoxicity, reactive oxygen species (ROS) production and pro-inflammatory response in both cell lines. We demonstrated that PLGA NPs are good candidates for negative control NPs and SiO2 NPs were revealed to be the best benchmark NPs. Coating of Fe3O4 with sodium oleate, a known biocompatible compound, led to an unexpected increase in cytotoxicity. Moreover, 16HBE cells are more sensitive than A549 cells and propidium iodide uptake is a more sensitive cytotoxicity test than WST-1. The measurement of oxidative stress does not systematically allow us to predict cellular responses and different other cellular endpoints should also be addressed. We conclude that a battery of assays and cell lines are necessary to accurately evaluate the pulmonary effects of NPs and that PLGA and SiO2 NPs are suitable candidates respectively for negative and positive controls.
authors.affiliation: Unit of Functional and Adaptive Biology (BFA), CNRS EAC 4413, Laboratory of Molecular and Cellular Responses to Xenobiotics (RMCX), University Paris Diderot , Sorbonne Paris Cité, 75205 Paris, Cedex 13 , France.
authors.forename: Rina
authors.initials: R
authors.lastname: Guadagnini
authors.forename: Kevin
authors.initials: K
authors.lastname: Moreau
authors.forename: Salik
authors.initials: S
authors.lastname: Hussain
authors.forename: Francelyne
authors.initials: F
authors.lastname: Marano
authors.forename: Sonja
authors.initials: S
authors.lastname: Boland
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D018836:Inflammation Mediators; D017382:Reactive Oxygen Species
keywords: Nanomedicine; nanotoxicology; oxidative stress; pro-inflammatory response; pulmonary toxicity