Biofunctional Peptide-Modified Extracellular Vesicles Enable Effective Intracellular Delivery via the Induction of Macropinocytosis

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 ind...

Full description

Saved in:
Bibliographic Details
Published in:Processes 2021-02, Vol.9 (2), p.224
Main Author: Nakase, Ikuhiko
Format: Article
Language:English
Subjects:
Actin
Arginine
Brain research
Cell activation
Clustering
Coils
Communication
Cytotoxicity
Dendritic cells
Diabetic retinopathy
Disease
Drug delivery systems
Epidermal growth factor receptors
Exosomes
Extracellular vesicles
Glycoproteins
Homeostasis
Intracellular
Kinases
Lectins
Leucine
Leucine zipper proteins
Ligands
Membranes
Metastasis
MicroRNAs
Multiple myeloma
Pancreatic cancer
Peptides
pH effects
Proteins
Proteoglycans
Signal transduction
Tumors
Vesicles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2227-9717
2227-9717
DOI:10.3390/pr9020224