The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells
AbstractExtracellular vesicles (EVs) are lipid membrane-bound particles involved in cell-to-cell communication through a delivery of regulatory molecules essential for physiological processes. Since EVs efficiently vectorize specific cargo molecules, they have been proposed as suitable vehicles for...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2162161 |
| _version_ | 1797260985534251008 |
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| author | Stefania Zuppone Natasa Zarovni Riccardo Vago |
| author_facet | Stefania Zuppone Natasa Zarovni Riccardo Vago |
| author_sort | Stefania Zuppone |
| collection | DOAJ |
| description | AbstractExtracellular vesicles (EVs) are lipid membrane-bound particles involved in cell-to-cell communication through a delivery of regulatory molecules essential for physiological processes. Since EVs efficiently vectorize specific cargo molecules, they have been proposed as suitable vehicles for therapeutic agents. Drug loading into EVs can be achieved by active, exogenous strategies or by genetic modifications of vesicle-producing cells. With the aim to produce EVs conveying therapeutic proteins, we genetically engineered and compared HEK293 to tumor cells. Tetraspanin-based RFP fusions were found to be more stable and preferentially sorted into EVs in HEK293. EVs isolated from genetically modified HEK293 cells media were captured by cancer cells, efficiently delivering their cargo. Cathepsin B cleavage site introduced between CD9/CD81 and RFP was recognized by tumor specific proteases allowing the release of the reporter protein. Our results indicate HEK293 cells as a preferential system for the production of EVs and pave the way to the development of nano-platforms for the efficient delivery of therapeutic proteins and prodrugs to tumor cells. |
| first_indexed | 2024-03-08T23:31:45Z |
| format | Article |
| id | doaj.art-694fa528f43742f788ee19883cb57f2a |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-24T23:34:01Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-694fa528f43742f788ee19883cb57f2a2024-03-15T14:22:17ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642023-12-0130110.1080/10717544.2022.2162161The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cellsStefania Zuppone0Natasa Zarovni1Riccardo Vago2Urological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milano, ItalyExosomics S.p.A, Siena, ItalyUrological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milano, ItalyAbstractExtracellular vesicles (EVs) are lipid membrane-bound particles involved in cell-to-cell communication through a delivery of regulatory molecules essential for physiological processes. Since EVs efficiently vectorize specific cargo molecules, they have been proposed as suitable vehicles for therapeutic agents. Drug loading into EVs can be achieved by active, exogenous strategies or by genetic modifications of vesicle-producing cells. With the aim to produce EVs conveying therapeutic proteins, we genetically engineered and compared HEK293 to tumor cells. Tetraspanin-based RFP fusions were found to be more stable and preferentially sorted into EVs in HEK293. EVs isolated from genetically modified HEK293 cells media were captured by cancer cells, efficiently delivering their cargo. Cathepsin B cleavage site introduced between CD9/CD81 and RFP was recognized by tumor specific proteases allowing the release of the reporter protein. Our results indicate HEK293 cells as a preferential system for the production of EVs and pave the way to the development of nano-platforms for the efficient delivery of therapeutic proteins and prodrugs to tumor cells.https://www.tandfonline.com/doi/10.1080/10717544.2022.2162161Extracellular vesiclesEVscargo sortingtetraspanin-based fusion proteinscathepsin B-controlled release |
| spellingShingle | Stefania Zuppone Natasa Zarovni Riccardo Vago The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells Drug Delivery Extracellular vesicles EVs cargo sorting tetraspanin-based fusion proteins cathepsin B-controlled release |
| title | The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells |
| title_full | The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells |
| title_fullStr | The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells |
| title_full_unstemmed | The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells |
| title_short | The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells |
| title_sort | cell type dependent sorting of cd9 and cd81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells |
| topic | Extracellular vesicles EVs cargo sorting tetraspanin-based fusion proteins cathepsin B-controlled release |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2162161 |
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