Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan Fibrosis
Abstract Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202200856 |
| _version_ | 1818177514389897216 |
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| author | Qiang Long Zehua Liu Qianwen Shao Hongpeng Shi Shixing Huang Chenyu Jiang Bei Qian Yiming Zhong Xiaojun He Xiaogang Xiang Yang Yang Bing Li Xiaoxiang Yan Qiang Zhao Xiaoli Wei Hélder A. Santos Xiaofeng Ye |
| author_facet | Qiang Long Zehua Liu Qianwen Shao Hongpeng Shi Shixing Huang Chenyu Jiang Bei Qian Yiming Zhong Xiaojun He Xiaogang Xiang Yang Yang Bing Li Xiaoxiang Yan Qiang Zhao Xiaoli Wei Hélder A. Santos Xiaofeng Ye |
| author_sort | Qiang Long |
| collection | DOAJ |
| description | Abstract Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast‐targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic‐co‐glycolic) acid cores, these nanoparticles, termed fibroblast membrane‐camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor‐β, interleukin (IL)‐11, IL‐13, and IL‐17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof‐of‐concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad‐spectrum therapy for fibrosis management. |
| first_indexed | 2024-12-11T20:33:18Z |
| format | Article |
| id | doaj.art-6f2974aabc8240b58904a871649dfa30 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-11T20:33:18Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-6f2974aabc8240b58904a871649dfa302022-12-22T00:51:45ZengWileyAdvanced Science2198-38442022-07-01921n/an/a10.1002/advs.202200856Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan FibrosisQiang Long0Zehua Liu1Qianwen Shao2Hongpeng Shi3Shixing Huang4Chenyu Jiang5Bei Qian6Yiming Zhong7Xiaojun He8Xiaogang Xiang9Yang Yang10Bing Li11Xiaoxiang Yan12Qiang Zhao13Xiaoli Wei14Hélder A. Santos15Xiaofeng Ye16Department of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Biomedical Engineering, W.J. Kolff Institute for Biomedical Engineering and Materials Science University Medical Center Groningen/University of Groningen Ant. Deusinglaan 1 Groningen 9713 AV The NetherlandsDepartment of Pharmacology School of Basic Medical Sciences Fudan University Shanghai 200032 ChinaDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Infectious Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Thoracic Surgery Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200000 ChinaDepartment of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200000 ChinaDepartment of Cardiovascular Medicine Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Pharmacology School of Basic Medical Sciences Fudan University Shanghai 200032 ChinaDepartment of Biomedical Engineering, W.J. Kolff Institute for Biomedical Engineering and Materials Science University Medical Center Groningen/University of Groningen Ant. Deusinglaan 1 Groningen 9713 AV The NetherlandsDepartment of Cardiovascular Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaAbstract Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast‐targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic‐co‐glycolic) acid cores, these nanoparticles, termed fibroblast membrane‐camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor‐β, interleukin (IL)‐11, IL‐13, and IL‐17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof‐of‐concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad‐spectrum therapy for fibrosis management.https://doi.org/10.1002/advs.202200856fibrosismyofibroblastnanoparticlesprofibrotic cytokine |
| spellingShingle | Qiang Long Zehua Liu Qianwen Shao Hongpeng Shi Shixing Huang Chenyu Jiang Bei Qian Yiming Zhong Xiaojun He Xiaogang Xiang Yang Yang Bing Li Xiaoxiang Yan Qiang Zhao Xiaoli Wei Hélder A. Santos Xiaofeng Ye Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan Fibrosis Advanced Science fibrosis myofibroblast nanoparticles profibrotic cytokine |
| title | Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan Fibrosis |
| title_full | Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan Fibrosis |
| title_fullStr | Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan Fibrosis |
| title_full_unstemmed | Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan Fibrosis |
| title_short | Autologous Skin Fibroblast‐Based PLGA Nanoparticles for Treating Multiorgan Fibrosis |
| title_sort | autologous skin fibroblast based plga nanoparticles for treating multiorgan fibrosis |
| topic | fibrosis myofibroblast nanoparticles profibrotic cytokine |
| url | https://doi.org/10.1002/advs.202200856 |
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