Journal
ACS NANO
Volume 12, Issue 7, Pages 6830-6842Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b02053
Keywords
extracellular vesicles; liposomes; fusion; polyethylene glycol; drug delivery
Categories
Funding
- ITMO-Inserm Plan Cancer
- Servier Laboratories
- Ecole de l'INSERM-Lilliane Bettencourt
- PhD Program Frontieres du Vivant (FdV) - Cursus Bettencourt
- Association Francaise contre les Myopathies (AFM) [20123]
- Fondation pour la Recherche Medicale (FRM)
- Labex Who am I?
- University of Bordeaux, CNRS [UMR 5248]
- Phenix, University Pierre and Marie Curie, CNRS [UMR 8234]
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Extracellular vesicles (EVs) are recognized as nature's own carriers to transport macromolecules throughout the body. Hijacking this endogenous communication system represents an attractive strategy for advanced drug delivery. However, efficient and reproducible loading of EVs with therapeutic or imaging agents still represents a bottleneck for their use as a drug delivery system. Here, we developed a method for modifying cell-derived EVs through their fusion with liposomes containing both membrane and soluble cargoes. The fusion of EVs with functionalized liposomes was triggered by polyethylene glycol (PEG) to create smart biosynthetic hybrid vectors. This versatile method proved to be efficient to enrich EVs with exogenous lipophilic or hydrophilic compounds, while preserving their intrinsic content and biological properties. Hybrid EVs improved cellular delivery efficiency of a chemotherapeutic compound by a factor of 3-4, as compared to the free drug or the drug-loaded liposome precursor. On one side, this method allows the biocamouflage of liposomes by enriching their lipid bilayer and inner compartment with biogenic molecules. On the other side, the proposed fusion strategy enables efficient EV loading, and the pharmaceutical development of EVs with adaptable activity and drug delivery property.
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