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. 2024 Apr 10;16(14):17069-17079.
doi: 10.1021/acsami.3c14592. Epub 2024 Apr 2.

Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery of Therapeutic Molecules

Kenta Morimoto  1 , Jojiro Ishitobi  1 , Kosuke Noguchi  1 , Ryoichi Kira  1 , Yukiya Kitayama  2 , Yuto Goto  2 , Daisuke Fujiwara  1 , Masataka Michigami  1 , Atsushi Harada  2 , Tomoka Takatani-Nakase  3   4 , Ikuo Fujii  1 , Shiroh Futaki  5 , Masamitsu Kanada  6   7 , Ikuhiko Nakase  1
Affiliations

Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery of Therapeutic Molecules

Kenta Morimoto et al. ACS Appl Mater Interfaces. .

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), transfer bioactive molecules from donor to recipient cells in various pathophysiological settings, thereby mediating intercellular communication. Despite their significant roles in extracellular signaling, the cellular uptake mechanisms of different EV subpopulations remain unknown. In particular, plasma membrane-derived MVs are larger vesicles (100 nm to 1 μm in diameter) and may serve as efficient molecular delivery systems due to their large capacity; however, because of size limitations, receptor-mediated endocytosis is considered an inefficient means for cellular MV uptake. This study demonstrated that macropinocytosis (lamellipodia formation and plasma membrane ruffling, causing the engulfment of large fluid volumes outside cells) can enhance cellular MV uptake. We developed experimental techniques to induce macropinocytosis-mediated MV uptake by modifying MV membranes with arginine-rich cell-penetrating peptides for the intracellular delivery of therapeutic molecules.

Keywords: arginine-rich cell-penetrating peptides; endocytosis; exosomes; extracellular vesicles; macropinocytosis; microvesicles; peptide modification.

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Conflict of interest statement

The authors declare no competing financial interest.

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