Relating Cytotoxicity, Zinc Ions, and Reactive Oxygen in ZnO Nanoparticle–Exposed Human Immune Cells

Abstract

Although zinc oxide (ZnO) nanoparticles (NPs) have been widely formulated in sunscreens, the relationship between reactive oxygen species (ROS) generation induced by these particles, zinc ions, and cytotoxicity is not clearly understood. This study explores whether these factors can be accurately quantified and related. The study demonstrates a strong correlation between ZnO NP-induced cytotoxicity and free intracellular zinc concentration (R (2) = .945) in human immune cells, indicating a requirement for NP dissolution to precede cytotoxicity. In addition, although direct exposure to ZnO NPs was found to induce cytotoxicity at relatively high concentrations, indirect exposure (via dialysis) was not cytotoxic, even at extremely high concentrations, highlighting a requirement for NP-to-cell contact. Elevated levels of ROS present in NP-exposed cells also correlated to both cytotoxicity and intracellular free zinc. Although the addition of antioxidant was able to reduce ROS, cytotoxicity to ZnO NPs was unaffected, suggesting ROS may be, in part, a result of cytotoxicity rather than a causal factor. This study highlights both the requirement and role of intracellular dissolution of zinc nanomaterials to elicit a cytotoxic response. This response is only partially ROS dependent, and therefore, modification of NP uptake and their intracellular solubility are key components in modulating the bioactivity of ZnO NPs.

Phytoextract-mediated synthesis of zinc oxide nanoparticles using aqueous leaves extract of Ipomoea pes-caprae (L).R.br revealing its biological properties and photocatalytic activity

“…The zinc ions might explain ZnO-induced cytotoxic and apoptotic activity. Zinc ions released from ZnO materials induce oxidative stressmediated cell death [7][8][9], and the strong correlation between ZnO NPs-induced cytotoxicity and free zinc ion concentration also suggests a requirement for ZnO dissolution for effective cytotoxicity [10]. A number of studies have reported the toxicity of ZnO materials, and their potential to induce cell death has been explored in cancer biology [7,11].…”

Toxicity of nanomaterials found in human environment

“…The nanoparticles were located exclusively in the cytoplasmic region. Shen et al 52 have reported cytotoxicity of ZnO nanoparticles on human immune cells. Their study shows a strong correlation between the cytotoxicity induced by ZnO nanoparticles and free intracellular zinc concentration.…”

Calcium ions rescue human lung epithelial cells from the toxicity of zinc oxide nanoparticles

“…Therefore, the toxicity of ZnO NPs is thought to be attributed to the NPs themselves. It also has been suggested that Zn ions released from ZnO NPs form zincphosphate-carbonate nanosized precipitate in culture medium (Turney et al, 2012), and this precipitate might protect cells from extracellular soluble zinc (Shen et al, 2013).…”

“…ZnO induces protective proteins, such as methallothioneins, against oxidative stress, and is occupied by the protective proteins. This occupation results in free transition metal ions, such as iron and copper, which induces a Fentontype reaction and increases ROS production (Krezel et al, 2007;Shen et al, 2013).…”

“…There are conflicting reports regarding whether the toxicity of ZnO NPs is owing to the release of Zn ions (Deng et al, 2009;Franklin et al, 2007;Song et al, 2010;Vandebriel and De Jong, 2012;Xia et al, 2008;Yang et al, 2010;Zhang et al, 2014) or whether the ZnO NPs themselves are toxic Moos et al, 2010;Shen et al, 2013).…”