Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylation
Radiation-induced fibrosis (RIF) is a major complication following radiotherapy treatment. Macrophages are the key regulators of inflammatory responses and have emerged as critical targets for the prevention of fibrosis. This study evaluated the efficacy of PEGylated phosphatidylserine-containing li...
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KeAi Communications Co., Ltd.
2025-10-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X2500249X |
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| author | Gyeung Mi Seon In Gul Kim Sun Woo Um Eun-Jae Chung Hyeong-Cheol Yang |
| author_facet | Gyeung Mi Seon In Gul Kim Sun Woo Um Eun-Jae Chung Hyeong-Cheol Yang |
| author_sort | Gyeung Mi Seon |
| collection | DOAJ |
| description | Radiation-induced fibrosis (RIF) is a major complication following radiotherapy treatment. Macrophages are the key regulators of inflammatory responses and have emerged as critical targets for the prevention of fibrosis. This study evaluated the efficacy of PEGylated phosphatidylserine-containing liposomes (PEG-PSLs) in mitigating RIF by modulating macrophage activity. PEG-PSLs influenced the polarization of bone marrow-derived macrophages (BMDMs), reducing the expression levels of inflammatory cytokines and fibrosis-associated markers. These effects were observed within a specific PEGylation range, with the greatest reduction achieved at 1–1.5mol% PEG. Analysis of the IL-4-induced JAK-STAT signaling pathway indicated that the PEG-PSL-mediated suppression occurred at or beyond the point of JAK-1 phosphorylation. In in vitro fibrosis assays, PEG-PSLs reduced fibroblast-to-myofibroblast and epithelial-to-mesenchymal transitions when co-cultured with BMDMs. In vivo studies using a rat model of esophageal irradiation demonstrated that PEG-PSLs effectively attenuated fibrotic progression, preserved tissue architecture, and enhanced muscle regeneration. These findings indicate the potential of partially PEGylated phosphatidylserine liposomes as therapeutic agents for mitigating post-irradiation esophageal fibrosis. |
| format | Article |
| id | doaj-art-e24dcb858e68487085cc56ee9b16c9fe |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-10-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-e24dcb858e68487085cc56ee9b16c9fe2025-08-24T05:13:46ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-10-015257458710.1016/j.bioactmat.2025.06.021Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylationGyeung Mi Seon0In Gul Kim1Sun Woo Um2Eun-Jae Chung3Hyeong-Cheol Yang4Department of Dental Biomaterials Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of KoreaDepartment of Dental Biomaterials Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea; Corresponding author. Department of Otorhinolaryngology-Head and Neck Surgery, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of KoreaDepartment of Dental Biomaterials Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea; Corresponding author.Radiation-induced fibrosis (RIF) is a major complication following radiotherapy treatment. Macrophages are the key regulators of inflammatory responses and have emerged as critical targets for the prevention of fibrosis. This study evaluated the efficacy of PEGylated phosphatidylserine-containing liposomes (PEG-PSLs) in mitigating RIF by modulating macrophage activity. PEG-PSLs influenced the polarization of bone marrow-derived macrophages (BMDMs), reducing the expression levels of inflammatory cytokines and fibrosis-associated markers. These effects were observed within a specific PEGylation range, with the greatest reduction achieved at 1–1.5mol% PEG. Analysis of the IL-4-induced JAK-STAT signaling pathway indicated that the PEG-PSL-mediated suppression occurred at or beyond the point of JAK-1 phosphorylation. In in vitro fibrosis assays, PEG-PSLs reduced fibroblast-to-myofibroblast and epithelial-to-mesenchymal transitions when co-cultured with BMDMs. In vivo studies using a rat model of esophageal irradiation demonstrated that PEG-PSLs effectively attenuated fibrotic progression, preserved tissue architecture, and enhanced muscle regeneration. These findings indicate the potential of partially PEGylated phosphatidylserine liposomes as therapeutic agents for mitigating post-irradiation esophageal fibrosis.http://www.sciencedirect.com/science/article/pii/S2452199X2500249XRadiation-induced esophageal fibrosisPEGylated phosphatidylserine liposomesMacrophage polarizationImmunomodulationTissue regeneration |
| spellingShingle | Gyeung Mi Seon In Gul Kim Sun Woo Um Eun-Jae Chung Hyeong-Cheol Yang Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylation Bioactive Materials Radiation-induced esophageal fibrosis PEGylated phosphatidylserine liposomes Macrophage polarization Immunomodulation Tissue regeneration |
| title | Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylation |
| title_full | Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylation |
| title_fullStr | Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylation |
| title_full_unstemmed | Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylation |
| title_short | Mitigation of radiation-induced esophageal fibrosis by macrophage-targeted phosphatidylserine-containing liposomes with partial PEGylation |
| title_sort | mitigation of radiation induced esophageal fibrosis by macrophage targeted phosphatidylserine containing liposomes with partial pegylation |
| topic | Radiation-induced esophageal fibrosis PEGylated phosphatidylserine liposomes Macrophage polarization Immunomodulation Tissue regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X2500249X |
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