Selective cytotoxic effect of ZnO nanoparticles on glioma cells

Abstract

In this study we examined the cytotoxic effect of ZnO nanoparticles on various human cancer and normal cells. We found that the ZnO nanoparticles exerted a cytotoxic effect on the human glioma cell lines A172, U87, LNZ308, LN18, and LN229, whereas no cytotoxic effect was observed on normal human astrocytes. Similarly, the ZnO nanoparticles induced cell death in breast and prostate cancer cell lines while no major effect was observed in the respective normal breast and prostate cell lines. Using the fl uorescent dye 2,7-dichlorofl uorescein diacetate, we found that treatment of the glioma cells with ZnO nanoparticles induced a large increase in the generation of reactive oxygen species (ROS) and treatment of the cells with N-acetyl cysteine decreased the cytotoxic effect of the ZnO nanoparticles. In contrast, a smaller effect on ROS generation was observed in the normal astrocytes. These results suggest that ZnO nanoparticles may be employed as a selective cytotoxic agent for the eradication of cancer cells.

Developing a Novel Embryo–Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics

“…7 and 8), which is the opposite of what we hypothesized would occur based on the in vitro data. However, the exposure concentrations used in the zebrafish xenograft assay were lower than the effective inhibitory concentrations in in vitro studies, 23,39,40 and we also identified that the ZnO NP agglomerated and underwent considerable dissolution (*47%-50%) when prepared in water (data previously published 28 ). Therefore, we cannot distinguish whether this increase in glioblastoma proliferation is due to a low-exposure NP effect, an ionic effect, or a combination of both.…”

“…Our short, 3-day assay allowed us to identify that this ZnO NP is unstable and slightly enhances glioblastoma growth in vivo. These results, in addition to evidence that ZnO NPs seem to only be effective at extremely high concentrations (*62 and 814 mg/L for instance) in in vitro assays, 39,40 suggest that these ZnO NPs in their current state are not a good candidate for future preclinical assessment against glioblastoma in mammalian models. These results illustrate how this short assay successfully combines the rapid economy of in vitro assays with the relevance of slower in vivo rodent assays to aid advances in drug and nanotherapeutic development.…”

“…These ZnO NPs were selected for our assay because of *28-to 35-fold preferential toxicity to cancerous T cells relative to normal peripheral blood mononuclear cells in vitro 23 and existing literature demonstrates that other ZnO NPs selectively inhibit glioblastoma proliferation in culture. 39,40 However, these in vitro anticancer effects are often seen at high exposure concentrations (mg/L or mM levels), which may call into question the relevancy of the results. Yet, it was not known if this selective toxicity would be conserved in vivo.…”

“…The high ZnO NP exposure concentrations used in the in vitro studies 23,39,40 caused toxicity in the embryo-larval zebrafish assay. At lower, nontoxic exposure concentrations (0.156-1.25 mg/L), the ZnO NPs slightly enhanced glioblastoma proliferation and migration/invasion compared with the vehicle control (Figs.…”

Damage of lipopolysaccharides in outer cell membrane and production of ROS-mediated stress within bacteria makes nano zinc oxide a bactericidal agent

“…Importantly, hexagonal structure of ZNP with (101) plane, the highest intense one, confirmed the growth along [0001] direction which might have impact on bacterial system (Huang et al 2008). Several studies have suggested, two possible mechanisms could be involved in the interaction between nanoparticles and bacteria-(a) the production of increased levels of ROS, mostly hydroxyl radicals and singlet oxygen (Ostrovsky et al 2009) and (b) deposition of the nanoparticles on the surface of bacteria or accumulation of nanoparticles either in the cytoplasm or in the periplasmic From our experimental results, we speculated that ZNP is first bound with hydrophilic counterpart of LPS resulting in some sort of deformation within OM. LPS is known to give first line of defence to E. coli cell from foreign substances; ZNP damaged the LPS which is present at the outer side of OM of E. coli.…”