A novel surface functionalization platform to prime extracellular vesicles for targeted therapy and diagnostic imaging
| Autor: | Besmira Sabani, Michael Brand, Ina Albert, Joelle Inderbitzin, Fritz Eichenseher, Mathias Schmelcher, Jack Rohrer, Rainer Riedl, Steffi Lehmann |
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| Rok vydání: | 2023 |
| Předmět: |
Targeted drug delivery
Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering Drug nanocarrier Extracellular Vesicles 615: Pharmakologie und Therapeutik Surface functionalization Diagnostic imaging Molecular Medicine General Materials Science Structure-based drug design Extracellular vesicle 610.28: Biomedizin Biomedizinische Technik |
| Zdroj: | Nanomedicine: Nanotechnology, Biology and Medicine. 47:102607 |
| ISSN: | 1549-9634 |
| Popis: | Extracellular vesicles (EVs), nanovesicles released by cells to effectively exchange biological information, are gaining interest as drug delivery system. Yet, analogously to liposomes, they show short blood circulation times and accumulation in the liver and the spleen. For tissue specific delivery, EV surfaces will thus have to be functionalized. We present a novel platform for flexible modification of EVs with target-specific ligands based on the avidin-biotin system. Genetic engineering of donor cells with a glycosylphosphatidylinositol-anchored avidin (GPI-Av) construct allows the isolation of EVs displaying avidin on their surface, functionalized with any biotinylated ligand. For proof of concept, GPI-Av EVs were modified with i) a biotinylated antibody or ii) de novo designed and synthesized biotinylated ligands binding carbonic anhydrase IX (CAIX), a membrane associated enzyme overexpressed in cancer. Functionalized EVs showed specific binding and uptake by CAIX-expressing cells, demonstrating the power of the system to prepare EVs for cell-specific drug delivery. |
| Databáze: | OpenAIRE |
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