Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation
Abstract Ulcerative colitis (UC) is a complex and chronic inflammatory bowel disease whose pathogenesis involves genetic and environmental factors, which poses a challenge for treatment. Here, we have designed an innovative integrated therapeutic strategy using Lactobacillus acidophilus extracellula...
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BMC
2025-04-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03376-0 |
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| author | Chenyang Cui Jiaze Tang Jie Chen Beining Zhang Ruonan Li Qiang Zhang Chunjing Qiu Rongchen Chen Geng Min Zhaowei Sun Haibo Weng |
| author_facet | Chenyang Cui Jiaze Tang Jie Chen Beining Zhang Ruonan Li Qiang Zhang Chunjing Qiu Rongchen Chen Geng Min Zhaowei Sun Haibo Weng |
| author_sort | Chenyang Cui |
| collection | DOAJ |
| description | Abstract Ulcerative colitis (UC) is a complex and chronic inflammatory bowel disease whose pathogenesis involves genetic and environmental factors, which poses a challenge for treatment. Here, we have designed an innovative integrated therapeutic strategy using Lactobacillus acidophilus extracellular vesicles (EVs) to encapsulate UiO-66-NH2 nanoparticles bounded with TNF-α siRNA (EVs@UiO-66-NH2@siRNA) for UC treatment. This system shows superior affinity to inflammation-related cells due to the Lactobacillus acidophilus EVs can maintain immune homeostasis by regulating the secretion of cytokines in vitro. siRNA can specifically target the key inflammatory TNF-α in UC and silence its gene expression, thereby regulating the process of inflammatory response. After oral administration, EVs@UiO-66-NH2@siRNA demonstrates an accurate delivery of TNF-α siRNA to colonize the colon site and exerts a siRNA therapeutic effect by inhibiting the expression of TNF-α, which alleviates the intestinal inflammation in DSS-induced UC model. Moreover, this system can modulate the types and compositional structures of gut microbiota and metabolites to achieve an anti-inflammatory phenotype, which is helpful for the repair of intestinal homeostasis. We also have proved that UiO-66-NH2 nanoparticles exhibit a high loading capacity for TNF-α siRNA and good pH responsiveness, improving the potent release of siRNA in colon tissue. Collectively, the EVs@UiO-66-NH2@siRNA nano-delivery system demonstrate a feasible combination therapeutic strategy for UC through gut microecology modulation, immune regulation and TNF-α siRNA silence, which may provide a potential targeted treatment approach for inflammatory bowel disease. Graphical Abstract |
| format | Article |
| id | doaj-art-7f4eb06ca70d4b57a866bf7f5f1b95ff |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-7f4eb06ca70d4b57a866bf7f5f1b95ff2025-08-20T03:53:46ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123112110.1186/s12951-025-03376-0Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulationChenyang Cui0Jiaze Tang1Jie Chen2Beining Zhang3Ruonan Li4Qiang Zhang5Chunjing Qiu6Rongchen Chen7Geng Min8Zhaowei Sun9Haibo Weng10School of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversityDepartment of Critical Care Medicine, The Fifth Affiliated Hospital of Zhengzhou UniversityHenan Key Laboratory of Helicobacter Pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversityAbstract Ulcerative colitis (UC) is a complex and chronic inflammatory bowel disease whose pathogenesis involves genetic and environmental factors, which poses a challenge for treatment. Here, we have designed an innovative integrated therapeutic strategy using Lactobacillus acidophilus extracellular vesicles (EVs) to encapsulate UiO-66-NH2 nanoparticles bounded with TNF-α siRNA (EVs@UiO-66-NH2@siRNA) for UC treatment. This system shows superior affinity to inflammation-related cells due to the Lactobacillus acidophilus EVs can maintain immune homeostasis by regulating the secretion of cytokines in vitro. siRNA can specifically target the key inflammatory TNF-α in UC and silence its gene expression, thereby regulating the process of inflammatory response. After oral administration, EVs@UiO-66-NH2@siRNA demonstrates an accurate delivery of TNF-α siRNA to colonize the colon site and exerts a siRNA therapeutic effect by inhibiting the expression of TNF-α, which alleviates the intestinal inflammation in DSS-induced UC model. Moreover, this system can modulate the types and compositional structures of gut microbiota and metabolites to achieve an anti-inflammatory phenotype, which is helpful for the repair of intestinal homeostasis. We also have proved that UiO-66-NH2 nanoparticles exhibit a high loading capacity for TNF-α siRNA and good pH responsiveness, improving the potent release of siRNA in colon tissue. Collectively, the EVs@UiO-66-NH2@siRNA nano-delivery system demonstrate a feasible combination therapeutic strategy for UC through gut microecology modulation, immune regulation and TNF-α siRNA silence, which may provide a potential targeted treatment approach for inflammatory bowel disease. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03376-0Ulcerative colitisLactobacillus acidophilus EVsTNF-α SiRNAUiO-66-NH2Targeted gene therapy |
| spellingShingle | Chenyang Cui Jiaze Tang Jie Chen Beining Zhang Ruonan Li Qiang Zhang Chunjing Qiu Rongchen Chen Geng Min Zhaowei Sun Haibo Weng Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation Journal of Nanobiotechnology Ulcerative colitis Lactobacillus acidophilus EVs TNF-α SiRNA UiO-66-NH2 Targeted gene therapy |
| title | Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation |
| title_full | Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation |
| title_fullStr | Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation |
| title_full_unstemmed | Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation |
| title_short | Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation |
| title_sort | lactobacillus acidophilus extracellular vesicles coated uio 66 nh2 sirna nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation |
| topic | Ulcerative colitis Lactobacillus acidophilus EVs TNF-α SiRNA UiO-66-NH2 Targeted gene therapy |
| url | https://doi.org/10.1186/s12951-025-03376-0 |
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