ArticleBMC biotechnology2022
αvβ3-targeted sEVs for efficient intracellular delivery of proteins using MFG-E8.
Article in BMC biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Bioengineering of extracellular vesicles with scaffold proteins for drug delivery.Journal of nanobiotechnology · 2026Review
- Oral Microcapsules Encapsulating Endometrial Regenerative Cell-Derived Exosomes Promote Intestinal Epithelial Barrier Repair and Ameliorate Experimental Colitis.International journal of nanomedicine · 2026Article
- Precision Engineering of Extracellular Vesicles as Programmable Carriers for mRNA Therapeutics.International journal of nanomedicine · 2026Review
- Generation of Cellular Biofactories for Scalable Production of Surface-Engineered Extracellular Vesicles via CRISPR Genome Editing.bioRxiv : the preprint server for biology · 2025Article
- An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration.Nature communications · 2025Article
- Extracellular Vesicles in Peripheral Nerve Regeneration: From Biology to Therapeutic Engineering.International journal of nanomedicine · 2025Review
- Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects.Theranostics · 2024Article
- Engineered EVs designed to target diseases of the CNS.Journal of controlled release : official journal of the Controlled Release Society · 2023Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSmall extracellular vesicles (sEVs) are nanometer-sized membranous particles shed by many types of cells and can transfer a multitude of cargos between cells. Recent studies of sEVs have been focusing on their potential to be novel drug carriers due to natural composition and other promising characteristics. However, there are challenges in sEVs-based drug delivery, one of which is the inefficient loading of drugs into sEVs, especially for large biomolecules.
resultsIn this study, we proposed a membrane-associated protein, milk fat globule-epidermal growth factor 8 protein (MFG-E8), to produce αvβ3-targeted sEVs with high delivery efficiency of interested protein. MFG-E8 is a secreted protein with NH2-terminal epidermal growth factor (EGF)-like domains, containing an Arg-Gly-Asp(RGD) sequence that binds αvβ3 and αvβ5 integrins, and COOH terminal domains C1 and C2, which can bind to lipid membrane with strong affinity. Firstly, we transiently expressed MFG-E8 in HEK293F cells and found that this protein could be secreted and adhere to the cell membrane. The recombinant MFG-E8 is also found to locate at the outer membrane of sEVs. Then we generated engineered sEVs by expressing high levels of the EGFP fused to MFG-E8 in HEK293F cells and showed that MFG-E8 could increase the delivery efficiency of EGFP into sEVs. Further delivery of Gaussia luciferase (GL) by fusion expression with MFG-E8 in donor cells demonstrated that target proteins fused with MFG-E8 still kept their activity. Finally, we identified the sEVs' target to integrin αvβ3 by comparing the transfection efficiency with MFG-E8 loaded sEVs (MFG-E8-sEVs) in αvβ3 positive cells and αvβ3 negative cells. Analysis showed higher target protein could transfect into αvβ3 positive cells with MFG-E8-sEVs than with EGFP loaded sEVs (EGFP-sEVs), meaning the engineered sEVs with MFG-E8 not only could increase the delivery of target protein into sEVs, but also could target the αvβ3 positive cells.
conclusionThis study suggests that recombinant MFG-E8 is an ideal protein to increasingly deliver the drug into sEVs and give sEVs the ability to target the αvβ3 positive cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.