Jornal de Nanomedicina e Nanotecnologia

Abstrato

Surface Coatings Protect against the In vitro Toxicity of Zinc Oxide Nanoparticles in Human Hepatic Stellate Cells

Megan J Osmond-McLeod, Yalchin Oytam, Ronald IW Osmond, Fariborz Sobhanmanesh and Maxine J McCall

Coatings applied to the surfaces of zinc oxide (ZnO) nanoparticles have been shown to decrease the capacity of uncoated nanoparticles to generate free radicals, as well as to reduce their solubility, and may be utilized in safetyby- design approaches to decrease ZnO nanoparticle toxicity. The liver is a target organ for ZnO nanoparticles, or ionic zinc released from ZnO nanoparticles, whether the route of entry is by dermal absorption, ingestion, injection or inhalation. Liver injury and fibrosis have been demonstrated in vivo in response to ZnO nanoparticle treatment, and cell injury has also been shown in vitro using immortalized hepatocyte cell lines. Despite their activation being a critical step for liver fibrosis, however, the response of human hepatic stellate cells (hHSCs) to ZnO nanoparticles has not yet been reported. Here, hHSCs were treated with four types of commercially-available ZnO nanoparticles suspended in cell culture medium. Two types were uncoated nanoparticles of different sizes, and the other two types with similar particle size carried different surface coatings. Cells were also treated with pre-dissolved ZnSO4 to provide a comparison of the cellular responses induced by ionic zinc. A systems biology approach was utilized whereby the activation of cell signaling pathways, changes in the transcriptome, and alterations in cellular function were assessed over a 24 h period. Treatment with both types of uncoated ZnO nanoparticles mobilized pathways and responses centered on cellular stress, survival, and apoptosis. Both surface coatings conferred almost complete protection against ZnO nanoparticle-induced cytotoxicity. Ionic zinc had little effect on these cells indicating that toxicity is mainly induced by the nanoparticles. The results presented here support the use of surface coatings in commercial applications of ZnO nanoparticles where there is human exposure.