Effect of engineered metal oxide nanoparticles on biological systems: an in vitro and in vivo approach

Abstract

Wide application of metal oxide engineered nanoparticles (ENPs) in catalysis, dyes, cosmetics, paints, biosensors, drug delivery, food packaging and as anticancerous agents has increased the risk of human exposure to these nanoparticles. Once ingested or inhaled, the ENPs can enter various cells of the body including the immune cells. Based on their industrial applications, ZnO and Cr2O3 ENPs are the most widely used. Therefore, the present study was aimed to assess the in vitro and in vivo immunotoxicity of ZnO ENPs and to determine the genotoxic and apoptotic effect of Cr2O3 ENPs in human cells. The study also elucidated the molecular mechanism of ENPs induced toxicity in the mammalian system. The in vitro investigation of the immunotoxic potential of ZnO ENPs using human monocytic cell line demonstrated an increase in pro-inflammatory cytokines. ZnO ENPs also induced oxidative and nitrosative stress in human monocytes, leading to increased inflammatory response via activation of redox sensitive NF-kB and MAPK signalling. The in vivo studies using the mouse model were conducted to determine age dependent ZnO ENPs induced immunotoxicity in BALB/c mice. Also, it was determined whether toxicity is due to ENPs or its ions through dissolution studies of ZnO ENPs in different conditions. The lung is one of the main exposure routes to nanomaterialstherefore, the present study was also designed to determine the genotoxic and apoptotic effect of Cr2O3 ENPs in human lung epithelial cells (A549). The study elucidated the molecular mechanism of its toxicity. Cr2O3 ENPs led to DNA damage, which was deduced by comet assay and cytokinesis block micronucleus assay. The reactive oxygen species led to a decrease in mitochondrial membrane potential and an increase in the ratio of BAX/Bcl-2 demonstrating mitochondria-mediated apoptosis induced by Cr2O3 ENPs. The present study provides valuable insights into the cellular interactions of ENPs and the underlying molecular mechanism of their toxicity. The results suggest that the indiscriminate use of ENPs in cosmetics, paints and other consumer goods should be avoided and guidelines should be implemented for ENPs usage.