Nanotoxicology of Metal Oxide Nanoparticles

Since the manufacture and use of nanoparticles are increasing, humans are more likely to be exposed occupationally or via consumer products and the environment. However, so far toxicity data for most manufactured nanoparticles are limited. The aim of this study was to investigate and compare different nanoparticles and nanotubes regarding cytotoxicity and ability to cause DNA damage and oxidative stress. The study was focused on different metal oxide particles (CuO, TiO2, ZnO, CuZnFe2O4, Fe3O4, Fe2O3), and the toxicity was compared to that of carbon nanoparticles and multiwalled carbon nanotubes (MWCNT). The human lung epithelial cell line A549 was exposed to the particles, and cytotoxicity was analyzed using trypan blue staining. DNA damage and oxidative lesions were determined using the comet assay, and intracellular production of reactive oxygen species (ROS) was measured using the oxidation-sensitive fluoroprobe 2',7'-dichlorofluorescin diacetate (DCFH-DA). The results showed that there was a high variation among different nanoparticles concerning their ability to cause toxic effects. CuO nanoparticles were most potent regarding cytotoxicity and DNA damage. The toxicity was likely not explained by Cu ions released to the cell medium. These particles also caused oxidative lesions and were the only particles that induced an almost significant increase (p = 0.058) in intracellular ROS. ZnO showed effects on cell viability as well as DNA damage, whereas the TiO2 particles (a mix of rutile and anatase) only caused DNA damage. For iron oxide particles (Fe3O4, Fe2O3), no or low toxicity was observed, but CuZnFe2O4 particles were rather potent in inducing DNA lesions. Finally, the carbon nanotubes showed cytotoxic effects and caused DNA damage in the lowest dose tested. The effects were not explained by soluble metal impurities. In conclusion, this study highlights the in vitro toxicity of CuO nanoparticles.

Virus infections pose significant global health challenges, especially in view of the fact that the emergence of resistant viral strains and the adverse side effects associated with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chemical and physical properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human imunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the production of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses.

As the production of nanoparticles of ZnO, TiO2 and CuO is increasing, their (eco)toxicity to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus was studied with a special emphasis on product formulations (nano or bulk oxides) and solubilization of particles. Our innovative approach based on the combination of traditional ecotoxicology methods and metal-specific recombinant biosensors allowed to clearly differentiate the toxic effects of metal oxides per se and solubilized metal ions. Suspensions of nano and bulk TiO2 were not toxic even at 20 g l(-1). All Zn formulations were very toxic: L(E)C50 (mg l(-1)) for bulk ZnO, nanoZnO and ZnSO4.7H2O: 1.8, 1.9, 1.1 (V. fischeri); 8.8, 3.2, 6.1 (D. magna) and 0.24, 0.18, 0.98 (T. platyurus), respectively. The toxicity was due to solubilized Zn ions as proved with recombinant Zn-sensor bacteria. Differently from Zn compounds, Cu compounds had different toxicities: L(E)C50 (mg l(-1)) for bulk CuO, nano CuO and CuSO4: 3811, 79, 1.6 (V. fischeri), 165, 3.2, 0,17 (D. magna) and 95, 2.1, 0.11 (T. platyurus), respectively. Cu-sensor bacteria showed that toxicity to V. fischeri and T. platyurus was largely explained by soluble Cu ions. However, for Daphnia magna, nano and bulk CuO proved less bioavailable than for bacterial Cu-sensor. This is the first evaluation of ZnO, CuO and TiO2 toxicity to V. fischeri and T. platyurus. For nano ZnO and nano CuO this is also a first study for D. magna.