Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells
Abstract Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03125-3 |
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| author | Markus Bergqvist Kyong-Su Park Nasibeh Karimi Lijuan Yu Cecilia Lässer Jan Lötvall |
| author_facet | Markus Bergqvist Kyong-Su Park Nasibeh Karimi Lijuan Yu Cecilia Lässer Jan Lötvall |
| author_sort | Markus Bergqvist |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor “lymphocyte function-associated antigen-1” (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18). The LFA-1 receptor was strongly overexpressed on the EVs released by the transfected cells. We further loaded these EVs with a therapeutic peptide, targeting myeloid differentiation primary response 88 (Myd88; EVMyd88), through a developed EV open-and-close procedure. Myd88 is a downstream common intracellular messenger for most TLR-receptors. EV expression of LFA-1 increases EV binding to ICAM-1-expressing cells, an effect that was dose-dependently inhibited by a specific neutralizing ICAM-1 antibody. Further, activated human endothelial cells treated with LFA-1 EVMyd88 had increased uptake of these EVs, resulting in dose-dependent inhibition of induced release of IL-8, presumably by targeting Myd88. We conclude that LFA-1-expressing EVMyd88 may be a candidate suitable for delivering therapeutic peptides in inflammatory diseases associated with TLR-activation. Graphical Abstract |
| format | Article |
| id | doaj-art-a014a5481ca1447dac2358ec0852cb16 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-a014a5481ca1447dac2358ec0852cb162025-02-02T12:41:18ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123111610.1186/s12951-025-03125-3Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cellsMarkus Bergqvist0Kyong-Su Park1Nasibeh Karimi2Lijuan Yu3Cecilia Lässer4Jan Lötvall5Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of GothenburgKrefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of GothenburgKrefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of GothenburgKrefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of GothenburgKrefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of GothenburgKrefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of GothenburgAbstract Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor “lymphocyte function-associated antigen-1” (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18). The LFA-1 receptor was strongly overexpressed on the EVs released by the transfected cells. We further loaded these EVs with a therapeutic peptide, targeting myeloid differentiation primary response 88 (Myd88; EVMyd88), through a developed EV open-and-close procedure. Myd88 is a downstream common intracellular messenger for most TLR-receptors. EV expression of LFA-1 increases EV binding to ICAM-1-expressing cells, an effect that was dose-dependently inhibited by a specific neutralizing ICAM-1 antibody. Further, activated human endothelial cells treated with LFA-1 EVMyd88 had increased uptake of these EVs, resulting in dose-dependent inhibition of induced release of IL-8, presumably by targeting Myd88. We conclude that LFA-1-expressing EVMyd88 may be a candidate suitable for delivering therapeutic peptides in inflammatory diseases associated with TLR-activation. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03125-3ExosomesGenetic engineeringIntegrin aLIntegrin b2TargetingPeptide loading |
| spellingShingle | Markus Bergqvist Kyong-Su Park Nasibeh Karimi Lijuan Yu Cecilia Lässer Jan Lötvall Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells Journal of Nanobiotechnology Exosomes Genetic engineering Integrin aL Integrin b2 Targeting Peptide loading |
| title | Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells |
| title_full | Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells |
| title_fullStr | Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells |
| title_full_unstemmed | Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells |
| title_short | Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells |
| title_sort | extracellular vesicle surface engineering with integrins itgal itgb2 to specifically target icam 1 expressing endothelial cells |
| topic | Exosomes Genetic engineering Integrin aL Integrin b2 Targeting Peptide loading |
| url | https://doi.org/10.1186/s12951-025-03125-3 |
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