Toxicity Studies On Combined Pollutants Of Typical Nanomaterials And Environmental Heavy Metals Or Chlorine Disinfectant

Engineering nanomaterials(ENMs)are widely used in various fields such as electronic devices,medicine and health,aerospace,environmental protection and biotechnology due to their various excellent properties in physical and chemical aspects.The rapid development and wide application of nanotechnology have made ENMs a new type of pollutant that exists in large numbers in the environment,which has led to a greatly increased exposure of nanoparticles(NPs)to other pollutants or organisms in the environment.In the past decade,people have conducted a lot of research on the toxic effects of nanomaterials(such as carbon-based nanomaterials,metal oxide/sulfide nanomaterials,etc.).The toxic effects of many nanomaterials are related to the oxidative stress induced by reactive oxygen species(ROS).Other pollutants in the environment usually also increase the level of oxidative stress in cells by combining with biological ligands,thereby exhibiting toxic effects,such as organic pollutants,heavy metal ions,and disinfectants,which are excessively accumulated in the organism It will pose a risk of ecotoxicity and even endanger human health.NPs will inevitably interact with coexisting pollutants in the environment to produce compound toxic effects.Therefore,it is necessary to study the compound toxic effects and toxic mechanisms of NPs-environmental pollutants.The research on the compound toxicity effects of NPs-environmental pollutants in this project mainly focuses on the three models of NPs-environmental pollutants interaction,namely:the effect of co-exposure after NPs adsorbs environmental pollutants on the compound toxicity;sequential exposure to NPs and The influence of environmental pollutants on compound toxicity;the influence of environmental transformation of NPs under the action of environmental pollutants on compound toxicity.Each part will select reasonable NPs and environmental pollutants for research based on needs.When studying the effect of co-exposure on composite toxicity of NPs after adsorbing environmental pollutants,the nanocomposite pollutants composed of carbon(CNPs)or zinc oxide(ZnONPs)and hexavalent chromium(?)were selected as the research object,and nanocomposite pollution was explored.The mechanism of the toxicity of substances on human lung epithelial cells A549;to study the effects of sequential exposure to NPs and environmental pollutants on the combined toxicity,we deliberately selected low-toxic carbon nanotubes(MWCNTs)as the research object,and did not cause significant toxicity in MWCNTs Under the premise,study the similarities and differences of the compound toxicity effects of subsequent exposure to heavy metal ions such as Pb(?),Cu(?),Cr(?));copper sulfide nanoparticles(CuSNPs)are used to study the environmental transformation of NPs under the action of environmental pollutants The best material for the effects of complex toxicity,because it will release Cu2+ under the action of disinfectants and cause the risk of complex toxicity effects.The implementation of the project provides new research methods and theoretical models for evaluating the compound toxicity effects of NPs—environmental pollutants in various situations,and provides theoretical foundation and technical support for the safe production and application of nanomaterials.The first part belongs to the study of the effects of co-exposure of NPs with pollutants on the composite toxicity based on the properties of nanomaterials with large specific surface area and easy adsorption of pollutants.This section takes the nanocomposite pollutants composed of carbon(CNPs)or zinc oxide(ZnONPs)core material nanoparticles and hexavalent chromium Cr(?)as the research object,and explores the toxic effects of nanocomposite pollutants on human lung epithelial cells A549 mechanism.Six kinds of nanocomposites with CNPs and ZnONPs as core materials were prepared,and each core material was loaded with three environmentally relevant concentrations of Cr(?).Through a comparative study of the toxic effects of two core materials in nanocomposite pollutants,it is found that:1)The interaction between nanomaterials and cell membranes plays a key role in the cytotoxicity of nanocomposite pollutants.ZnONPs aggravate the cytotoxicity of nanocomposite pollutants by destroying the integrity of cell membranes.The cell's toxic response to Cr(?)is reflected in the cell survival rate,oxidative stress response and mitochondrial function;in addition,CNPs and ZnONPs enter the cell in different ways,and CNPs are mainly through caveolin-mediated endocytosis Enter the cell,while ZnONPs enter the cell mainly through macropinocytosis.Therefore,CNPs and ZnONPs cause a significant difference in the uptake of Cr(?)by the cell.2)The interaction between nanomaterials and coexisting pollutants plays a key role in the cytotoxicity of nanocomposite pollutants.Compared with ZnONPs core materials,CNPs core materials can reduce Cr(?)to Cr(?)with lower toxicity.Thereby reducing the cytotoxicity of Cr(?);in addition,compared with CNPs-Cr(?)nanocomposite,ZnONPs-Cr(?)nanocomposite can release more Cr after entering the cell and being swallowed by lysosomes(?),which also resulted in the enhanced cytotoxicity of the ZnONPs-Cr(?)nanocomposite.This study deeply analyzes the two factors that affect the cytotoxicity of nanocomposite pollutants,namely the interaction between nanomaterials and cells,and the interaction between nanomaterials and coexisting pollutants.It provides a thorough understanding of different nanomaterials and coexisting pollutants.The combined cytotoxicity is of great value.In the second part,we study the effect of sequential exposure of NPs and pollutants on the compound toxicity to simulate the occupational exposure of workers to nanomaterials.Nanomaterials have no effect on workers' health,but may increase or decrease subsequent exposure to environmental pollutants.Health effects.In this work,single-walled carbon nanotubes(SWCNTs)and carboxy-modified single-walled carbon nanotubes(SWCNT-COOHs)were used to pretreat human monocytic leukemia cells THP-1.After pretreatment,the cells showed no obvious toxicity,and then The effects of these two pretreatments on the cytotoxicity of heavy metal ions(Pb(?),Cu(?),Cr(?))were compared.The cells were pretreated with SWCNTs and SWCNT-COOHs for 12 h.According to the results of SDS-PAGE,the level of carbon tubes in the cells slowly increased at this stage.Findings:1)Although pretreatment has no effect on the morphology and survival rate of cells,according to the LDH release experiment,Hoechst 33342/PI cell double staining method and scanning electron microscopy images,SWCNTs have caused serious damage to cell membranes,while SWCNTCOOHs The effect on the cell membrane is very weak.By comparing the uptake level and toxicity response of unpretreated and pretreated cells to metal ions,it is found that:2)The pretreatment of SWCNTs exacerbates the damage of cell membranes,which leads to the effects of cells on Cu(?)and Pb(?).The uptake and oxidative stress response of the three heavy metal ions of Cr(?)and Cr(?)are enhanced,and the cell survival rate is reduced;however,SWCNT-COOHs has almost no effect on the integrity of cell membranes,so SWCNT-COOHs pretreatment does not change the cell's effect on Cu(?).),Pb(?)and Cr(?)intake,when appropriately reducing the toxic response of cells to heavy metal ions.3)The adsorption experiment shows that the adsorption effect of SWCNT-COOHs on heavy metal ions is higher than that of SWCNTs,which is also one of the reasons that SWCNT-COOHs pretreatment reduces the cytotoxicity of heavy metal ions.To the best of our knowledge,this study reported for the first time how single-walled carbon nanotubes and modified single-walled carbon nanotubes were used to pre-treat cells before exposure to heavy metal ions and how to affect the cytotoxicity of heavy metal ions.Finally,the third part takes copper sulfide nanomaterials(CuSNPs)as an example to study the effect of environmental transformation on the toxicity of nanomaterials.CuSNPs are chosen as the research object because they are generally sulfide nanomaterials with low toxicity.This work studied the developmental toxicity of copper sulfide nanomaterials(CuSNPs)and the drinking water disinfectant sodium hypochlorite(NaClO)in the water environment on the developmental toxicity of zebrafish embryos,revealing that the chemical transformation between nanomaterials and coexisting pollutants is the influence An important factor in the toxic effect of nanocomposite pollutants.The selected exposure dose is 200 ?g/L CuSNPs and the US EPA recommended drinking water disinfection dose of 4 mg/L NaClO.The results of the study showed that:1)Except for the slightly delayed incubation time of zebrafish embryos,CuSNPs alone exposure did not have a significant effect on the growth and development of embryos,and when zebrafish embryos were exposed to CuSNPsNaClO nanocomposite pollutants,embryo growth The development is significantly inhibited.More than 50%of embryos clot and die within the chorion within 48 hours.This inhibition is significantly higher than the embryo toxicity caused by NaClO alone exposure;this is because:2)Under the oxidation of NaClO,The stability of CuSNPs is reduced,and the dissolved copper ion concentration is 24.01?g/L,which improves the bioavailability of copper in zebrafish;3)Metabonomics analysis shows that CuSNPs interferes with the metabolism of zebrafish embryos.However,NaClO has a serious damaging effect on the antioxidant damage and protein synthesis-related pathways in zebrafish;NaClO also up-regulates the expression of ABC transporters to accelerate the efflux of pollutants.However,through metabolomics analysis and in vivo experiments in zebrafish,it was found that the dissolution of copper ions in CuSNPsNaClO nanocomposite pollutants aggravated the membrane structure damage in zebrafish(up-regulation of glycerophospholipid metabolism,up-regulation of ABC transporter,apoptosis and Increased necrotic cells)and oxidative damage(increased MDA level,decreased SOD and CAT activity).This study points out that the stability and low toxicity of metal sulfides in water may be changed due to coexisting pollutants in the environment,and emphasizes the key role of chemical conversion between nanomaterials and coexisting pollutants in nanocomposite pollutants.The water environment risks of such nanocomposite pollutants combined exposure provide basic data.In summary,this project is based on the study of the compound toxicity effects of NPs—environmental pollutants,and mainly focuses on the three models of NPs—environmental pollutants interaction,namely:the effect of co-exposure after NPs adsorbs environmental pollutants on the compound toxicity;The effect of sequential exposure to NPs and environmental pollutants on compound toxicity;the effect of environmental transformation of NPs under the action of environmental pollutants on compound toxicity.The development of related work has provided experimental data for the exposure risk of nanocomposite pollution in the environment,provided new ideas for exploring the toxicity mechanism of nanocomposite pollutants,and provided theoretical support for the interpretation of related nanocomposite pollution exposure toxicity mechanisms.