Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles
Abstract Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39181-2 |
| _version_ | 1797806669016596480 |
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| author | Lixue Wang Guosheng Wang Wenjun Mao Yundi Chen Md. Mofizur Rahman Chuandong Zhu Peter M. Prisinzano Bo Kong Jing Wang Luke P. Lee Yuan Wan |
| author_facet | Lixue Wang Guosheng Wang Wenjun Mao Yundi Chen Md. Mofizur Rahman Chuandong Zhu Peter M. Prisinzano Bo Kong Jing Wang Luke P. Lee Yuan Wan |
| author_sort | Lixue Wang |
| collection | DOAJ |
| description | Abstract Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine. |
| first_indexed | 2024-03-13T06:10:47Z |
| format | Article |
| id | doaj.art-bf5ab3291395474baaa4e0192fa89dd2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T06:10:47Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-bf5ab3291395474baaa4e0192fa89dd22023-06-11T11:18:29ZengNature PortfolioNature Communications2041-17232023-06-0114111210.1038/s41467-023-39181-2Bioinspired engineering of fusogen and targeting moiety equipped nanovesiclesLixue Wang0Guosheng Wang1Wenjun Mao2Yundi Chen3Md. Mofizur Rahman4Chuandong Zhu5Peter M. Prisinzano6Bo Kong7Jing Wang8Luke P. Lee9Yuan Wan10Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese MedicineThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton UniversityThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton UniversityThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton UniversityThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton UniversityDepartment of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese MedicineThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton UniversityDeparment of General, Visceral and Transplantation Surgery, Section of Surgical Research, Heidelberg University HospitalDepartment of Oncology and Hematology, Yizheng Hospital of Nanjing Drum Tower Hospital GroupDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton UniversityAbstract Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine.https://doi.org/10.1038/s41467-023-39181-2 |
| spellingShingle | Lixue Wang Guosheng Wang Wenjun Mao Yundi Chen Md. Mofizur Rahman Chuandong Zhu Peter M. Prisinzano Bo Kong Jing Wang Luke P. Lee Yuan Wan Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles Nature Communications |
| title | Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles |
| title_full | Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles |
| title_fullStr | Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles |
| title_full_unstemmed | Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles |
| title_short | Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles |
| title_sort | bioinspired engineering of fusogen and targeting moiety equipped nanovesicles |
| url | https://doi.org/10.1038/s41467-023-39181-2 |
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