H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation
Abstract Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first‐line treatments for IBD have limited efficacy and sign...
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202308092 |
| _version_ | 1797215289804324864 |
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| author | Ting Jin Hongyang Lu Qiang Zhou Dongfan Chen Youyun Zeng Jiayi Shi Yanmei Zhang Xianwen Wang Xinkun Shen Xiaojun Cai |
| author_facet | Ting Jin Hongyang Lu Qiang Zhou Dongfan Chen Youyun Zeng Jiayi Shi Yanmei Zhang Xianwen Wang Xinkun Shen Xiaojun Cai |
| author_sort | Ting Jin |
| collection | DOAJ |
| description | Abstract Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first‐line treatments for IBD have limited efficacy and significant side effects. An innovative H2S‐releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO‐1, PI3K‐AKT, and RAS/MAPK/AP‐1, and inhibiting the p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management. |
| first_indexed | 2024-04-24T11:27:42Z |
| format | Article |
| id | doaj.art-607df34197bf438b8e2be2af7955a62a |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-24T11:27:42Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-607df34197bf438b8e2be2af7955a62a2024-04-10T13:10:12ZengWileyAdvanced Science2198-38442024-04-011114n/an/a10.1002/advs.202308092H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease ModulationTing Jin0Hongyang Lu1Qiang Zhou2Dongfan Chen3Youyun Zeng4Jiayi Shi5Yanmei Zhang6Xianwen Wang7Xinkun Shen8Xiaojun Cai9School and Hospital of Stomatology Wenzhou Medical University Wenzhou 325027 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou 325027 ChinaDepartment of Otolaryngology Ruian People's Hospital The Third Affiliated Hospital of Wenzhou Medical University Wenzhou 325016 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou 325027 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou 325027 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou 325027 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou 325027 ChinaSchool of Biomedical Engineering Research and Engineering Center of Biomedical Materials Anhui Medical University Hefei 230032 ChinaDepartment of Otolaryngology Ruian People's Hospital The Third Affiliated Hospital of Wenzhou Medical University Wenzhou 325016 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou 325027 ChinaAbstract Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first‐line treatments for IBD have limited efficacy and significant side effects. An innovative H2S‐releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO‐1, PI3K‐AKT, and RAS/MAPK/AP‐1, and inhibiting the p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management.https://doi.org/10.1002/advs.202308092colitisgut microbiotahydrogen sulfide gas therapyimmunoregulationpeptide dendrimer nanogel |
| spellingShingle | Ting Jin Hongyang Lu Qiang Zhou Dongfan Chen Youyun Zeng Jiayi Shi Yanmei Zhang Xianwen Wang Xinkun Shen Xiaojun Cai H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation Advanced Science colitis gut microbiota hydrogen sulfide gas therapy immunoregulation peptide dendrimer nanogel |
| title | H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation |
| title_full | H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation |
| title_fullStr | H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation |
| title_full_unstemmed | H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation |
| title_short | H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation |
| title_sort | h2s releasing versatile montmorillonite nanoformulation trilogically renovates the gut microenvironment for inflammatory bowel disease modulation |
| topic | colitis gut microbiota hydrogen sulfide gas therapy immunoregulation peptide dendrimer nanogel |
| url | https://doi.org/10.1002/advs.202308092 |
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