Effective extracellular vesicle-based intracellular delivery of an artificially encapsulated protein

Extracellular vesicles (EVs, exosomes) are approximately 30- to 200-nm-long vesicles that have received increased attention due to their role in cell-to-cell communication. Although EVs are highly anticipated to be a next-generation intracellular delivery tool because of their pharmaceutical advantages, including non-immunogenicity, their cellular uptake efficacy is low because of the repulsion of EVs and negatively charged cell membranes and size limitations in endocytosis.

Here, researchers from Osaka Prefecture University demonstrate a methodology for achieving enhanced cellular EV uptake using arginine-rich cell-penetrating peptides (CPPs) to induce active macropinocytosis. The induction of macropinocytosis via a simple modification to the exosomal membrane using stearylated octaarginine, which is a representative CPP, significantly enhanced the cellular EV uptake efficacy. Consequently, effective EV-based intracellular delivery of an artificially encapsulated ribosome-inactivating protein, saporin, in EVs was attained.

Schematic representation of the intracellular delivery of EVs


Objective therapeutic molecules are encapsulated in EVs by electroporation. EVs are then modified with stearyl-r8 peptide on EV membranes, resulting in the active induction of macropinocytosis and effective cellular uptake.

Nakase I, Noguchi K, Fujii I, Futaki S. (2016) Vectorization of biomacromolecules into cells using extracellular vesicles with enhanced internalization induced by macropinocytosis. Sci Rep 6:34937. [article]

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