The Toxicity Of Metal Oxide Nanomaterials Research

Copper oxide nanoparticles induce autophagic death in A549cells and can cause acute pulmonary injury in miceMetal oxide nanomaterials are among the most highly produced nanomaterials and their applications include catalysis, sensors, environmental remediation, and personal care products. High levels of these nanoparticles can be detected in the ambient air, especially in industrial regions, and they are major airborne pollutants in these areas. These ultrafine particles have a small aerodynamic diameter, therefore they can easily penetrate the alveolar region deep in the lungs, causing adverse pulmonary effects or exacerbating existing pulmonary diseases. In this study, cells were exposed to metal oxide nanomaterials such as copper oxide, silica and ferric oxide. Copper oxide caused the greatest amount of cytotoxicity in A549, H1650and CNE-2Z cells while the other metal oxide nanoparticles had little effect on the viability of these cells. Exposure to copper oxide did not induce apoptosis according to TUNEL results, neither was the cleavage of caspase3detected through western blotting. In addition, treatment with the pan-caspase inhibitor zVAD-fmk did not rescue cell death, suggesting that copper oxide induced cell death is caspase independent. In A549cells treated with copper oxide nanoparticles, the amount of LC3-Ⅱwas significantly elevated, and the use of autophagy inhibitors Wortmannin and3-MA significantly improved cell survival, suggesting that copper oxide nanoparticles may induce cytotoxicity through autophagy in A549cells. In order to study the toxic effects of these nanoparticles in vivo, C57BL/6were given metal oxide nanoparticles through I.T. Copper oxide nanoparticles induced the most severe pulmonary edema of all the metal oxide nanoparticles. Mice given300μ g copper oxide nanoparticles died within24h, indicating copper oxide causes acute toxicity. The level of IL-6was significantly elevated in BALF of mice treated with copper oxide nanoparticles, suggesting inflammation may play a crucial role in copper oxide nanoparticle induced lung injury and death. In this study, it is shown that copper oxide nanoparticles causes greater toxicity in cells and mice compared with other metal oxide nanomaterials. Copper oxide nanoparticles are often used as additives in coatings, plasticware, lubricants and textiles, as well as many other applications. Therefore, the study of copper oxide nanotoxicity and its mechanism need to be further evaluated. Drug screening of autophagy inhibitors3-Methyladenine (3-MA) is the most widely used autophagy inhibitor. But since it is used at very high concentrations to inhibit autophagy, it can target other kinases and influence other cellular processes. Therefore, it is very important to develop second generation autophagy inhibitors which are highly specific and can be used at low concentrations. Compound1,2,6,9and10are analogues derived from3-MA through chemical modification. PAMAM G3nanoparticles can induce autophagic death in A549cells, and we used this model to screen for the most potent autophagy inhibitor. Cell viability results showed that100μmol·L-1Compound10can alleviate PAMAM G3induced autophagic cell death, and is the most potent inhibitor of all candidates. In addition,300umol·L-1Compound9also showed inhibitory effect. Compound10and9have the potential to become members of the next generation of autophagy inhibitors, which are important tools for studying autophagy and may even be used in clinical treatment.