Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathway
Abstract Hypertrophic scar (HS) is one of the most common challenges in the field of plastic and reconstructive surgery. HS formation is associated with the abnormal activation of fibroblasts. These fibroblasts exhibit excessive proliferative and fibrotic behavior, which can be induced by glycolysis...
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BMC
2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03562-0 |
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| author | Xinxian Meng Zhixi Yu Shiqi Wu Wanyu Xu Yuzhen Tang Zixuan Chen Yixin Zhang Yunsheng Chen Zheng Zhang |
| author_facet | Xinxian Meng Zhixi Yu Shiqi Wu Wanyu Xu Yuzhen Tang Zixuan Chen Yixin Zhang Yunsheng Chen Zheng Zhang |
| author_sort | Xinxian Meng |
| collection | DOAJ |
| description | Abstract Hypertrophic scar (HS) is one of the most common challenges in the field of plastic and reconstructive surgery. HS formation is associated with the abnormal activation of fibroblasts. These fibroblasts exhibit excessive proliferative and fibrotic behavior, which can be induced by glycolysis dysregulation. Herein, self-assembled nanogels prepared by modifying IR808 with hyaluronic acid (termed HA-IR808) are introduced as selective glycolytic inhibitors to control HS formation through transdermal delivery to HS fibroblasts (HFs). HA-IR808 preferentially targets activated HFs and has a structure suitable for transdermal delivery. In vitro, HA-IR808 exhibits a glycolysis inhibition effect and regulates the fibrotic behavior and proliferation of HFs through energy depletion and macromolecule synthesis. In vivo, HA-IR808 penetrates the dermal layer, regulates glycolysis, and controls HS formation. Mechanistically, HA-IR808 regulates glycolysis by silencing the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway. In conclusion, this research elucidates a strategy for controlling HS formation via glycolysis regulation using self-assembled HA-IR808 nanogels to inhibit HF activation. Graphical abstract |
| format | Article |
| id | doaj-art-789a2786dee643ff9e2c7dc35ccac580 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-789a2786dee643ff9e2c7dc35ccac5802025-08-20T04:03:07ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123111610.1186/s12951-025-03562-0Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathwayXinxian Meng0Zhixi Yu1Shiqi Wu2Wanyu Xu3Yuzhen Tang4Zixuan Chen5Yixin Zhang6Yunsheng Chen7Zheng Zhang8Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Burn, Shanghai Burn Institute, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Hypertrophic scar (HS) is one of the most common challenges in the field of plastic and reconstructive surgery. HS formation is associated with the abnormal activation of fibroblasts. These fibroblasts exhibit excessive proliferative and fibrotic behavior, which can be induced by glycolysis dysregulation. Herein, self-assembled nanogels prepared by modifying IR808 with hyaluronic acid (termed HA-IR808) are introduced as selective glycolytic inhibitors to control HS formation through transdermal delivery to HS fibroblasts (HFs). HA-IR808 preferentially targets activated HFs and has a structure suitable for transdermal delivery. In vitro, HA-IR808 exhibits a glycolysis inhibition effect and regulates the fibrotic behavior and proliferation of HFs through energy depletion and macromolecule synthesis. In vivo, HA-IR808 penetrates the dermal layer, regulates glycolysis, and controls HS formation. Mechanistically, HA-IR808 regulates glycolysis by silencing the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway. In conclusion, this research elucidates a strategy for controlling HS formation via glycolysis regulation using self-assembled HA-IR808 nanogels to inhibit HF activation. Graphical abstracthttps://doi.org/10.1186/s12951-025-03562-0Hypertrophic scarGlycolysis regulationTransdermal deliveryFibroblastNanogels |
| spellingShingle | Xinxian Meng Zhixi Yu Shiqi Wu Wanyu Xu Yuzhen Tang Zixuan Chen Yixin Zhang Yunsheng Chen Zheng Zhang Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathway Journal of Nanobiotechnology Hypertrophic scar Glycolysis regulation Transdermal delivery Fibroblast Nanogels |
| title | Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathway |
| title_full | Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathway |
| title_fullStr | Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathway |
| title_full_unstemmed | Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathway |
| title_short | Self-assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the PI3K/Akt/mTOR pathway |
| title_sort | self assembled transdermal nanogels control scar formation by inhibiting fibroblast proliferation and fibrosis with glycolysis regulation via the pi3k akt mtor pathway |
| topic | Hypertrophic scar Glycolysis regulation Transdermal delivery Fibroblast Nanogels |
| url | https://doi.org/10.1186/s12951-025-03562-0 |
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