Toxicity of Silver-nanoparticles (NPs) and Silver-NP Based Hydrogel
|School||South China University of Technology|
|Keywords||Ag-NP-based hydrogel Ag-NP reproductive organ micro-pathology cytotoxicity DNA microarray|
Silver-nanoparticles (Ag-NPs) have stronger antibacterial activities compared with micro-silver particles, due to their small size, large surface, and high surface activity. They are being widely and earlier used in biological materials. Silver nanoparticle-based hydrogel (Ag-NP-Gel) is used for treating the cervicitis or the cervical erosion due to the antibacterial activities of Ag-NPs. Although Ag-NP-Gel has been used in clinical trials, the lack of information regarding biological safety evaluation and toxicology risk assessment remains an important issue. In order to study the toxicity of silver nanoparticle-based hydrogel, in vivo uptake and accumulation of Ag-NPs in reproductive organs, and micro-pathology of the tissues, as well as in vitro cytotoxicity after Ag-NPs-Gel exposure in rabbit and HeLa cells were investigated. To further study the toxicity and potential mechanisms of silver-NPs on primary cells, the cytotoxicity and global gene expression analysis using DNA microarray was also performed using syrian hamster embryo cells and rat embryo cells.The results showed that the silver-NPs content in some reproductive organs was increased to compare that in the control group after 6 days continuously exposure of Ag-NPs-Gel in the rabbit vagina administration, and micro-pathological changes in reproductive organs were observed, like mitochondria swelling, endoplasmic reticulum expansion, vacuole, chromatin concentration and micronucleation, etc.. The HeLa cells exposed to Ag-NPs-Gel also showed the accumulation of Ag-NPs, vacuole and micronuclei formation in the cells. These results suggested that the continuously use of Ag-NP-Gel possibly to cause micro-pathological level changes in the reproductive organs; and the observation of apoptosis, chromatin concentration and micronucleation in the reproductive organ tissues suggested that Ag-NPs-Gel may be increase the genotoxicity and reproductive toxicity risk. The results from micropathological changes of Ag-NPs exposed Syrian hamster embryo cells showed the accumulation of Ag-NPs, vacuole, micronucleation and nucleus disruption, etc., suggested that Ag-NPs induced cytotoxicity on primary embryo cells as well as that induced by Ag-NPs-Gel on HeLa cells. The results from DNA microarray analysis showed that there are 355 differential expression genes were discovered, and among them, 132 genes were up-regulated, 233 genes were down-regulated. These genes mainly correlated with stress response, immune response,cell growth, apoptosis, energy metabolism and signal transduction pathways, etc.. These changes on main signal pathways of the cells may be the important mechanisms of the Ag-NPs-induced micro-pathological changes in primary embryo cells.