The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles

Abstract

Understanding the possible role of physicochemical properties in determining the toxicity of ZnO nanomaterials (NMs) is crucial for the safe use of ZnO-based materials. In this study, we synthesized four types of ZnO NMs, and characterized them as ZnO nanorods (NRs; length 400-500 nm, diameter 150-200 nm), ZnO Mini-NRs (length 50-100 nm, diameter 15-20 nm), amorphous ZnO microspheres (a-ZnO MS) and crystalline ZnO MS (c-ZnO MS; the a/c-ZnO MS are nanoflowers with an extensive growth of sheet-like structures). ZnO NMs and ZnO Mini-NRs were significantly more cytotoxic than a/c-ZnO MS, and this trend was similar in both HepG2 cells and human umbilical vein endothelial cells. Intracellular reactive oxygen species was only modestly induced by c-ZnO MS, whereas intracellular Zn ions were dose-dependently increased in HepG2 cells by the exposure of all types of ZnO NMs. The expression of endoplasmic reticulum stress marker DDIT3 was induced following an order of ZnO NRs > a-ZnO MS > c-ZnO MS > ZnO Mini-NRs, and the apoptosis gene CASP12 was induced following an order of a-ZnO MS > ZnO NRs > c-ZnO MS > ZnO Mini-NRs. Combined, these results suggested that ZnO NM-induced cytotoxicity and expression of endoplasmic reticulum stress-apoptosis genes could be influenced by the size and shape of ZnO NMs.

Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress

“…The atomic force microscopy images (Figure A and B) indicate that ZnO NRs and ZnO Mini‐NRs are similar in topography. The X‐ray diffraction pattern of ZnO NRs and ZnO Mini‐NRs has been reported by us before, which corresponds to the well‐crystallized wurtzite ZnO (Yan et al, ).…”

“…The ZnO NMs used in this study were recently synthesized by us and named as ZnO NRs and ZnO Mini‐NRs according to the scanning electron microscopy images (Yan et al, ). Here the NMs were still denoted as ZnO NRs and ZnO Mini‐NRs throughout the manuscript in keeping with our previous publication, although the representative transmission electron microscopy images shown in Figure A and B indicate that both samples contained rod‐like structures (arrows in Figure ) and irregular particles (fingers in Figure ).…”

“…ZnO NRs and ZnO Mini‐NRs were synthesized by established methods and thoroughly characterized as we reported before (Yan et al, ). This study further used transmission electron microscopy (JEOL JEM‐2100, Tokyo, Japan) to investigate the morphology as well as atomic force microscopy (Bruker MultiMode 8, Santa Barbara, CA, USA) to investigate the topography of ZnO NMs, respectively.…”

“…Recently, we synthesized ZnO NMs (denoted as ZnO nanorods [NRs] and Mini‐NRs) and showed that the cytotoxicity of ZnO NRs to HepG2 cells could be related with ER stress, because ER stress‐apoptosis gene expression could be rapidly activated following toxic ZnO NR exposure (Yan, Long, Liu, & Cao, ). In this study, we further investigated the influence of PA on toxicity of these ZnO NMs to THP‐1 macrophages.…”

Effects of TiO2 nanoparticles on the life‐table parameters, antioxidant indices, and swimming speed of the freshwater rotifer Brachionus calyciflorus

“…The toxicity of most nanomaterials is mainly related to two mechanisms: physical stress or stimuli caused by size, shape, and surface properties of nanoparticles (Carnovale, Bryant, Shukla, & Bansal, 2016; Yan, Long, Liu, & Cao, 2019) and chemical toxicity by reactive oxygen species (ROS) (Armstrong & Bharali, 2013; Fu, Xia, Hwang, Ray, & Yu, 2014; Ma et al, 2014). In aquatic environments, nanomaterials induced overproduction of ROS, which then caused lipid peroxidation and damages to cell membranes (Tee, Ong, Bay, Ho, & Leong, 2016).…”