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Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery
Kenta Morimoto1, Jojiro Ishitobi1, Kosuke Noguchi1
1Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1, Gakuen-cho, Naka-ku, Sakai 599-8531, Osaka, Japan.
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.
Insights
Cellular uptake of microvesicles (MVs) is enhanced by macropinocytosis, a process involving cell membrane engulfment. This study modified MVs with peptides to improve intracellular delivery via macropinocytosis.
Area of Science:
- Cell Biology
- Biotechnology
- Nanomedicine
Background:
- Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are crucial for intercellular communication by transferring bioactive molecules.
- The precise mechanisms of cellular uptake for different EV subpopulations, especially larger MVs, are not fully understood.
- Receptor-mediated endocytosis is inefficient for cellular uptake of MVs due to their size.
Purpose of the Study:
- To investigate and enhance the cellular uptake mechanisms of microvesicles (MVs).
- To explore the role of macropinocytosis in MV cellular internalization.
- To develop strategies for efficient intracellular delivery of therapeutic molecules using MVs.
Main Methods:
- Induction of macropinocytosis through experimental techniques.
- Modification of MV membranes with arginine-rich cell-penetrating peptides.
- Assessment of MV uptake enhancement via macropinocytosis.
Main Results:
- Macropinocytosis significantly enhances the cellular uptake of microvesicles (MVs).
- Modified MVs demonstrated improved internalization through macropinocytosis-mediated pathways.
- The study provides a novel method for enhancing intracellular delivery of therapeutic payloads.
Conclusions:
- Macropinocytosis is a key mechanism for cellular uptake of MVs.
- Peptide modification of MVs can effectively leverage macropinocytosis for enhanced intracellular delivery.
- This approach holds potential for developing advanced drug delivery systems.
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