MoS_(2)nanosheets(NSs)are novel 2D nanomaterials(NMs)with potential uses in many areas,and therefore oral exposure route to MoS_(2)NSs is plausible.Currently,MoS_(2)NSs are considered as biocompatible NMs,but there is...MoS_(2)nanosheets(NSs)are novel 2D nanomaterials(NMs)with potential uses in many areas,and therefore oral exposure route to MoS_(2)NSs is plausible.Currently,MoS_(2)NSs are considered as biocompatible NMs,but there is lacking of systemic investigations to study the interactions of MoS_(2)NSs with intestinal cells.In this study,we exposed the 3D Caco-2 spheroids to MoS_(2)NSs or MoS_(2)powders(denoted as MoS_(2)-bulk),and investigated the potential adverse effects of MoS_(2)-materials based on transcriptomics and lipidomics analysis.As expected,both MoS_(2)NSs and MoS_(2)-bulk were dose-dependently internalized into 3D Caco-2 spheroids but did not induce cytotoxicity,membrane disruption or decrease of thiols.However,the Gene Ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analysis indicated that nutrient absorption and metabolism was decreased.One of the most significantly decreased KEGG pathways is fat digestion and absorption(map04975),and Western blotting analysis further showed that fatty acid binding protein 1 and apolipoprotein A1,key proteins involved in fat digestion and absorption,were down-regulated by MoS_(2)NSs or MoS_(2)-bulk.In addition,BODIPY 493/503 staining suggested that exposure to MoS_(2)NSs and MoS_(2)-bulk decreased lipid levels in the spheroids.However,lipidomics data indicated that MoS_(2)materials only decreased 8 lipid classes,including lysophosphatidylcholine,lysodimethylphosphatidylethanolamine,N-acylethanolamine,ceramide phosphoethanolamines,gangliosides,lysosphingomyelin and sulfatide,whereas most of the lipid classes were indeed increased.In addition,MoS_(2)NSs was more potent to decrease the lipid classes compared with MoS_(2)-bulk.Combined,the results from this study showed that MoS_(2)NSs and bulk materials were non-cytotoxic but altered lipid profiles in 3D Caco-2 spheroids.展开更多
基金financially supported by National Natural Science Foundation of China(No.51803055)Natural Science Foundation of Hunan Province(No.2019JJ50372)Hunan Provincial Key Research and Development Program(No.2018GK2062)。
文摘MoS_(2)nanosheets(NSs)are novel 2D nanomaterials(NMs)with potential uses in many areas,and therefore oral exposure route to MoS_(2)NSs is plausible.Currently,MoS_(2)NSs are considered as biocompatible NMs,but there is lacking of systemic investigations to study the interactions of MoS_(2)NSs with intestinal cells.In this study,we exposed the 3D Caco-2 spheroids to MoS_(2)NSs or MoS_(2)powders(denoted as MoS_(2)-bulk),and investigated the potential adverse effects of MoS_(2)-materials based on transcriptomics and lipidomics analysis.As expected,both MoS_(2)NSs and MoS_(2)-bulk were dose-dependently internalized into 3D Caco-2 spheroids but did not induce cytotoxicity,membrane disruption or decrease of thiols.However,the Gene Ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analysis indicated that nutrient absorption and metabolism was decreased.One of the most significantly decreased KEGG pathways is fat digestion and absorption(map04975),and Western blotting analysis further showed that fatty acid binding protein 1 and apolipoprotein A1,key proteins involved in fat digestion and absorption,were down-regulated by MoS_(2)NSs or MoS_(2)-bulk.In addition,BODIPY 493/503 staining suggested that exposure to MoS_(2)NSs and MoS_(2)-bulk decreased lipid levels in the spheroids.However,lipidomics data indicated that MoS_(2)materials only decreased 8 lipid classes,including lysophosphatidylcholine,lysodimethylphosphatidylethanolamine,N-acylethanolamine,ceramide phosphoethanolamines,gangliosides,lysosphingomyelin and sulfatide,whereas most of the lipid classes were indeed increased.In addition,MoS_(2)NSs was more potent to decrease the lipid classes compared with MoS_(2)-bulk.Combined,the results from this study showed that MoS_(2)NSs and bulk materials were non-cytotoxic but altered lipid profiles in 3D Caco-2 spheroids.
