LAPSE:2022.0065
Published Article
LAPSE:2022.0065
Biofunctional Peptide-Modified Extracellular Vesicles Enable Effective Intracellular Delivery via the Induction of Macropinocytosis
Ikuhiko Nakase
October 13, 2022
We previously reported that macropinocytosis (accompanied by actin reorganization, ruffling of the plasma membrane, and engulfment of large volumes of extracellular fluid) is an important process for the cellular uptake of extracellular vesicles, exosomes. Accordingly, we developed techniques to induce macropinocytosis by the modification of biofunctional peptides on exosomal membranes, thereby enhancing their cellular uptake. Arginine-rich cell-penetrating peptides have been shown to induce macropinocytosis via proteoglycans; accordingly, we developed peptide-modified exosomes that could actively induce macropinocytotic uptake by cells. In addition, the activation of EGFR induces macropinocytosis; based on this knowledge, we developed artificial leucine-zipper peptide (K4)-modified exosomes. These exosomes can recognize E3 sequence-fused EGFR (E3-EGFR), leading to the clustering and activation of E3-EGFR by coiled-coil formation (E3/K4), which induces cellular exosome uptake by macropinocytosis. In addition, modification of pH-sensitive fusogenic peptides (e.g., GALA) also enhances the cytosolic release of exosomal contents. These experimental techniques and findings using biofunctional peptides have contributed to the development of exosome-based intracellular delivery systems.
Keywords
biofunctional peptides, exosomes, intracellular delivery systems, macropinocytosis
Subject
Suggested Citation
Nakase I. Biofunctional Peptide-Modified Extracellular Vesicles Enable Effective Intracellular Delivery via the Induction of Macropinocytosis. (2022). LAPSE:2022.0065
Author Affiliations
Nakase I: Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan; NanoSquare Research Institute, Osaka Prefecture University, 1-2, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570,
Journal Name
Processes
Volume
9
Issue
2
First Page
224
Year
2021
Publication Date
2021-01-25
Published Version
ISSN
2227-9717
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Original Submission
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PII: pr9020224, Publication Type: Review
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LAPSE:2022.0065
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doi:10.3390/pr9020224
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Oct 13, 2022
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CC BY 4.0
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Oct 13, 2022
 
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Oct 13, 2022
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Original Submitter
Mina Naeini
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