Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusion
Abstract A major obstacle in knocking down oncogenes for tumor therapy is the efficient delivery of siRNA into the cytosolic spaces of cancer cells. Here, we genetically bioengineer biomimetic nanovesicles with tumor-recognition and enzyme-controlled membrane fusion functions for efficiently deliver...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61230-1 |
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| author | Lele Cui Yongsheng Cui Jing Liu Wei Li Mengdan Wu Xiawei Wei Ying Lai Peng Mi |
| author_facet | Lele Cui Yongsheng Cui Jing Liu Wei Li Mengdan Wu Xiawei Wei Ying Lai Peng Mi |
| author_sort | Lele Cui |
| collection | DOAJ |
| description | Abstract A major obstacle in knocking down oncogenes for tumor therapy is the efficient delivery of siRNA into the cytosolic spaces of cancer cells. Here, we genetically bioengineer biomimetic nanovesicles with tumor-recognition and enzyme-controlled membrane fusion functions for efficiently delivering small interfering RNA into cancer cells towards gene silencing tumor therapy. The siRNA@eS-BNVs are formulated by encapsulating siRNA inside the core and coating with genetically engineered HEK293TACE2- cell membranes encoded with functional S protein, which can recognize cancer cells and initiate membrane fusion when triggered by the enzyme. The siRNA@eS-BNVs demonstrate better efficacy for cytosolic siRNA delivery and RNA interference than conventional formulations. By intravenous injection, siRNA@eS-BNVs are highly accumulated in tumors and potently inhibited tumor and lung metastasis by simultaneously silencing the epidermal growth factor receptor gene in vivo. The cancer cell-targeting and enzyme-activatable nanovesicles provide a valuable strategy for effective and precise drug delivery. |
| format | Article |
| id | doaj-art-e9229b6cc3cd4258aa430bec4763bfd6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e9229b6cc3cd4258aa430bec4763bfd62025-08-20T04:01:41ZengNature PortfolioNature Communications2041-17232025-07-0116112010.1038/s41467-025-61230-1Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusionLele Cui0Yongsheng Cui1Jing Liu2Wei Li3Mengdan Wu4Xiawei Wei5Ying Lai6Peng Mi7Department of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Radiology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAbstract A major obstacle in knocking down oncogenes for tumor therapy is the efficient delivery of siRNA into the cytosolic spaces of cancer cells. Here, we genetically bioengineer biomimetic nanovesicles with tumor-recognition and enzyme-controlled membrane fusion functions for efficiently delivering small interfering RNA into cancer cells towards gene silencing tumor therapy. The siRNA@eS-BNVs are formulated by encapsulating siRNA inside the core and coating with genetically engineered HEK293TACE2- cell membranes encoded with functional S protein, which can recognize cancer cells and initiate membrane fusion when triggered by the enzyme. The siRNA@eS-BNVs demonstrate better efficacy for cytosolic siRNA delivery and RNA interference than conventional formulations. By intravenous injection, siRNA@eS-BNVs are highly accumulated in tumors and potently inhibited tumor and lung metastasis by simultaneously silencing the epidermal growth factor receptor gene in vivo. The cancer cell-targeting and enzyme-activatable nanovesicles provide a valuable strategy for effective and precise drug delivery.https://doi.org/10.1038/s41467-025-61230-1 |
| spellingShingle | Lele Cui Yongsheng Cui Jing Liu Wei Li Mengdan Wu Xiawei Wei Ying Lai Peng Mi Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusion Nature Communications |
| title | Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusion |
| title_full | Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusion |
| title_fullStr | Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusion |
| title_full_unstemmed | Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusion |
| title_short | Bioengineered nanovesicles for efficient siRNA delivery through ligand-receptor-mediated and enzyme-controlled membrane fusion |
| title_sort | bioengineered nanovesicles for efficient sirna delivery through ligand receptor mediated and enzyme controlled membrane fusion |
| url | https://doi.org/10.1038/s41467-025-61230-1 |
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