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.

• Nanomedicine
• nanotoxicology
• oxidative stress
• pro-inflammatory response
• pulmonary toxicity

Acknowledgements

Authors thank Dr Florent Busi for his kind help for RTqPCR; Imago Seine, imaging platform of Institut Jaques Monod and especially Nicole Boggetto for her assistance in flow cytometry.

Declaration of interest

The authors declare that there is no conflict of interests. This work was supported by the NanoTEST project (Contract EC FP7 number 201335) and grant N° R03/75-79 from “Ligue Nationale contre le Cancer (Comité Ile de France)” for acquisition of the flow cytometer.