Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury
Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is a common challenge in various clinical practices, yet effective therapies remain elusive. Endothelial injury plays a crucial role in the pathogenesis of renal IRI. Endothelial progenitor cells (EPCs) derived extracellular...
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Elsevier
2025-04-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425000869 |
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| author | Di Wu Wenjie Ma Liucheng Wang Chengcheng Long Silin Chen Jingyu Liu Yiguan Qian Jun Zhao Changcheng Zhou Ruipeng Jia |
| author_facet | Di Wu Wenjie Ma Liucheng Wang Chengcheng Long Silin Chen Jingyu Liu Yiguan Qian Jun Zhao Changcheng Zhou Ruipeng Jia |
| author_sort | Di Wu |
| collection | DOAJ |
| description | Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is a common challenge in various clinical practices, yet effective therapies remain elusive. Endothelial injury plays a crucial role in the pathogenesis of renal IRI. Endothelial progenitor cells (EPCs) derived extracellular vesicles (EVs) hold promise as cell-free therapies for treating renal IRI; however, their efficacy is limited by low delivery efficiency. In this study, we developed neutrophils (NEs) membrane-modified EVs (N-EVs) by exploiting the natural properties of NEs to target damaged endothelium. N-EVs inherited the characteristic membrane proteins of NEs along with the biological functions of EPCs-EVs. Results from in vitro and in vivo experiments demonstrated that N-EVs significantly enhanced the targeting efficiency of EVs towards IRI kidneys via P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, N-EVs effectively promoted the proliferation, migration, and tube-formation abilities of injured endothelial cells (ECs) and contributed to overall renal function improvement in IRI kidneys through targeted delivery of miR-21-5p. Additionally, N-EVs could restore damaged endothelial integrity, reduce cytokine release, and inhibit leukocyte infiltration, hence alleviating renal inflammation. In conclusion, our accessible engineering approach represents a promising strategy for treating renal IRI. Furthermore, this membrane hybrid modification can be tailored and optimized for broader applications in treating other diseases. |
| format | Article |
| id | doaj-art-c20256fd59a84dd09bec0a0247d293e8 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-c20256fd59a84dd09bec0a0247d293e82025-02-03T04:16:53ZengElsevierMaterials Today Bio2590-00642025-04-0131101528Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injuryDi Wu0Wenjie Ma1Liucheng Wang2Chengcheng Long3Silin Chen4Jingyu Liu5Yiguan Qian6Jun Zhao7Changcheng Zhou8Ruipeng Jia9Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, ChinaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, ChinaDepartment of Urology, Lianshui People's Hospital, Kangda College Affiliated to Nanjing Medical University, Jiang Su, 223400, ChinaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, ChinaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, ChinaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, ChinaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, ChinaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, ChinaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China; Corresponding author. Department of Urology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China; Corresponding author. Department of Urology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is a common challenge in various clinical practices, yet effective therapies remain elusive. Endothelial injury plays a crucial role in the pathogenesis of renal IRI. Endothelial progenitor cells (EPCs) derived extracellular vesicles (EVs) hold promise as cell-free therapies for treating renal IRI; however, their efficacy is limited by low delivery efficiency. In this study, we developed neutrophils (NEs) membrane-modified EVs (N-EVs) by exploiting the natural properties of NEs to target damaged endothelium. N-EVs inherited the characteristic membrane proteins of NEs along with the biological functions of EPCs-EVs. Results from in vitro and in vivo experiments demonstrated that N-EVs significantly enhanced the targeting efficiency of EVs towards IRI kidneys via P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, N-EVs effectively promoted the proliferation, migration, and tube-formation abilities of injured endothelial cells (ECs) and contributed to overall renal function improvement in IRI kidneys through targeted delivery of miR-21-5p. Additionally, N-EVs could restore damaged endothelial integrity, reduce cytokine release, and inhibit leukocyte infiltration, hence alleviating renal inflammation. In conclusion, our accessible engineering approach represents a promising strategy for treating renal IRI. Furthermore, this membrane hybrid modification can be tailored and optimized for broader applications in treating other diseases.http://www.sciencedirect.com/science/article/pii/S2590006425000869EngineeringExtracellular vesicleNeutrophilCell membraneRenoprotectionmiRNAs |
| spellingShingle | Di Wu Wenjie Ma Liucheng Wang Chengcheng Long Silin Chen Jingyu Liu Yiguan Qian Jun Zhao Changcheng Zhou Ruipeng Jia Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury Materials Today Bio Engineering Extracellular vesicle Neutrophil Cell membrane Renoprotection miRNAs |
| title | Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury |
| title_full | Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury |
| title_fullStr | Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury |
| title_full_unstemmed | Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury |
| title_short | Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury |
| title_sort | physically engineered extracellular vesicles targeted delivering mir 21 5p to promote renoprotection after renal ischemia reperfusion injury |
| topic | Engineering Extracellular vesicle Neutrophil Cell membrane Renoprotection miRNAs |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425000869 |
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