Modification of Extracellular Vesicles by Fusion with Liposomes for the Design of Personalized Biogenic Drug Delivery Systems

TLDR

Extracellular vesicles are natural carriers for macromolecules, and exploiting this system for drug delivery is attractive, yet efficient and reproducible loading remains a bottleneck. The authors developed a method to modify cell‑derived EVs by fusing them with liposomes that carry both membrane and soluble cargoes. PEG‑induced fusion of EVs with functionalized liposomes creates smart biosynthetic hybrid vectors. The fusion strategy efficiently loads EVs with lipophilic or hydrophilic compounds, preserves their intrinsic properties, boosts chemotherapeutic delivery 3–4×, and enables biocamouflage and adaptable drug‑delivery capabilities.

Abstract

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.