Acute lung injury(ALI)is a devastating inflammatory disease.MicroRNA155(miR155)in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1(SOC...Acute lung injury(ALI)is a devastating inflammatory disease.MicroRNA155(miR155)in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1(SOCS1)in ALI.Anti-miR155 oligonucleotide(AMO155)have been suggested as a potential therapeutic reagent for ALI.However,a safe and efficient carrier is required for delivery of AMO155 into the lungs for ALI therapy.In this study,cell membrane-derived nanovesicles(CMNVs)were produced from cell membranes of LA4 mouse lung epithelial cells and evaluated as a carrier of AMO155 into the lungs.For preparation of CMNVs,cell membranes were isolated from LA4 cells and CMNVs were produced by extrusion.Cholesterol-conjugated AMO155(AMO155c)was loaded into CMNVs and extracellular vesicles(EVs)by sonication.The physical characterization indicated that CMNVs with AMO155c(AMO155c/CMNV)were membrane-structured vesicles with a size of�120nm.The delivery efficiency and therapeutic efficacy of CMNVs were compared with those of EVs or polyethylenimine(25kDa,PEI25k).The delivery efficiency of AMO155c by CMNVs was similar to that by EVs.As a result,the miR155 levels were reduced by AMO155c/CMNV and AMO155c/EV.AMO155c/CMNV were administered intratracheally into the ALI models.The SOCS1 levels were increased more efficiently by AMO155c/CMNV than by the others,suggesting that miR155 effectively was inhibited by AMO155c/CMNV.In addition,the inflammatory cytokines were reduced more effectively by AMO155c/CMNV than they were by AMO155c/EV and AMO155c/PEI25k,reducing inflammation reactions.The results suggest that CMNVs are a useful carrier of AMO155c in the treatment of ALI.展开更多
基金supported by the Basic Science&Engineering Research Program(NRF-2022R1A2B5B01001920)the National Research Foundation,funded by the Ministry of Science and ICT in Korea.
文摘Acute lung injury(ALI)is a devastating inflammatory disease.MicroRNA155(miR155)in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1(SOCS1)in ALI.Anti-miR155 oligonucleotide(AMO155)have been suggested as a potential therapeutic reagent for ALI.However,a safe and efficient carrier is required for delivery of AMO155 into the lungs for ALI therapy.In this study,cell membrane-derived nanovesicles(CMNVs)were produced from cell membranes of LA4 mouse lung epithelial cells and evaluated as a carrier of AMO155 into the lungs.For preparation of CMNVs,cell membranes were isolated from LA4 cells and CMNVs were produced by extrusion.Cholesterol-conjugated AMO155(AMO155c)was loaded into CMNVs and extracellular vesicles(EVs)by sonication.The physical characterization indicated that CMNVs with AMO155c(AMO155c/CMNV)were membrane-structured vesicles with a size of�120nm.The delivery efficiency and therapeutic efficacy of CMNVs were compared with those of EVs or polyethylenimine(25kDa,PEI25k).The delivery efficiency of AMO155c by CMNVs was similar to that by EVs.As a result,the miR155 levels were reduced by AMO155c/CMNV and AMO155c/EV.AMO155c/CMNV were administered intratracheally into the ALI models.The SOCS1 levels were increased more efficiently by AMO155c/CMNV than by the others,suggesting that miR155 effectively was inhibited by AMO155c/CMNV.In addition,the inflammatory cytokines were reduced more effectively by AMO155c/CMNV than they were by AMO155c/EV and AMO155c/PEI25k,reducing inflammation reactions.The results suggest that CMNVs are a useful carrier of AMO155c in the treatment of ALI.
