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Updated: Mar 13, 2026

Visualizing Membrane Ruffle Formation using Scanning Electron Microscopy
Published on: May 27, 2021
Vectorization of biomacromolecules into cells using extracellular vesicles with enhanced internalization induced by
Ikuhiko Nakase1, Kosuke Noguchi1,2, Ikuo Fujii2
1Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, Naka-ku, Sakai, Osaka 599-8570, Japan.
Abstract:
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, we 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.
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