Abstract
BackgroundThe wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties.ResultsTHP-1 and BEAS-2B cells were exposed to 0–200 μg/mL MOx for 24 h, we found some toxic MOx including CoO, CuO, Ni2O3 and Co3O4, could induce reactive oxygen species (ROS) generation and cell death due to the toxic ion shedding and/or oxidative stress generation from the active surface of MOx internalized into lysosomes. We thus hypothesized that surface passivation could reduce or eliminate the toxicity of MOx. We experimented with a series of surface coating molecules and discovered that ethylenediamine tetra (methylene phosphonic acid) (EDTMP) could form stable hexadentate coordination with MOx. The coating layer can effectively reduce the surface activity of MOx with 85-99% decrease of oxidative potential, and 65-98% decrease of ion shedding. The EDTMP coated MOx show negligible ROS generation and cell death in THP-1 and BEAS-2B cells. The protective effect of EDTMP coating was further validated in mouse lungs exposed to 2 mg/kg MOx by oropharyngeal aspiration. After 40 h exposure, EDTMP coated MOx show significant decreases of neutrophil counts, lactate dehydrogenase (LDH) release, MCP-1, LIX and IL-6 in bronchoalveolar lavage fluid (BALF), compared to uncoated particles. The haematoxylin and eosin (H&E) staining results of lung tissue also show EDTMP coating could significantly reduce the pulmonary inflammation of MOx.ConclusionsThe surface reactivity of MOx including ion shedding and oxidative potential is the dominated physicochemical property that is responsible for the cytotoxicity induced by MOx. EDTMP coating could passivate the surface of MOx, reduce their cytotoxicity and pulmonary hazard effects. This coating would be an effective safe design approach for a broad spectrum of toxic MOx, which will facilitate the safe use of MOx in commercial nanoproducts.
Highlights
The wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety
Characterizing the surface reactivity of metal oxides (MOx) and determining their cytotoxicity First, we established a library of MOx including CoO, Ni2O3, Co3O4, CuO, which have been shown to induce cell death by oxidative stress mechanism, and TiO2 was used as negative control
Ethylenediamine tetra(methylenephosphonic acid) (EDTMP) coating shows a little interference on the cellular uptake levels of some MOx (Additional file 8: Figure S7), these inferences cannot explain the protective effects of EDTMP coating layer. These results suggested that the surface passivation rather than cellular uptake interference by EDTMP coating is responsible for the reduced cytotoxicity of all coated MOx, and EDTMP coating could be potentially used as a safe design approach for a broadspectrum of MOx
Summary
The wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, safe designs of MOx with reduced hazard potential are desired. Metal oxides (MOx) are the most produced nanomaterials because of their unique physicochemical properties including catalytic activity, antibacterial capability, chemical stability, electrical, thermal and mechanical characteristics. The increasing production as well as wide use of MOx has led to substantial concerns on their potential hazardous effects to both humans and environment [4]. The toxicity induced by MOx has been demonstrated to closely correlate with their surface properties such as electronic property (band gap), functional groups, dissolution, etc. We hypothesized that surface passivation could be an effective approach to engineer safe MOx
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