Modified extracellular vesicles for active induction and delivery of therapeutic molecules

Extracellular vesicles (EVs) play a crucial role as messengers, ferrying bioactive molecules between cells in various physiological and pathological contexts. EVs come in different flavors, including exosomes and microvesicles (MVs), each with its unique characteristics and functions. While their importance in intercellular communication is well-established, the mechanisms underlying the uptake of different EV subpopulations remain elusive.

A recent study by researchers at the Osaka Metropolitan University shed light on the cellular uptake mechanisms of EVs, particularly focusing on plasma membrane-derived MVs. Unlike exosomes, which are smaller and can be internalized through receptor-mediated endocytosis, MVs pose a unique challenge due to their larger size, ranging from 100 nm to 1 μm in diameter. Traditionally, it was believed that MV uptake via receptor-mediated endocytosis was inefficient due to size limitations.

However, the study revealed a surprising finding: macropinocytosis, a cellular process characterized by the formation of membrane protrusions called lamellipodia and the engulfment of large fluid volumes, plays a crucial role in enhancing MV uptake. This discovery opens new avenues for understanding how cells internalize larger EVs and underscores the versatility of cellular uptake mechanisms.

Building on this insight, the researchers developed experimental techniques to harness macropinocytosis for targeted MV uptake. By modifying MV membranes with arginine-rich cell-penetrating peptides, they were able to enhance the intracellular delivery of therapeutic molecules encapsulated within MVs. This innovative approach holds immense promise for the development of novel strategies for drug delivery and therapeutic interventions.

This study provides valuable insights into the intricate dance of intercellular communication mediated by EVs. By unraveling the mysteries of MV uptake mechanisms, these researchers have paved the way for exploiting EVs as efficient molecular delivery systems. As our understanding of EV biology continues to evolve, we can expect further breakthroughs in the field of cellular communication and therapeutics.

Morimoto K, Ishitobi J, Noguchi K, Kira R, Kitayama Y, Goto Y, Fujiwara D, Michigami M, Harada A, Takatani-Nakase T, Fujii I, Futaki S, Kanada M, Nakase I. (2024) Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery of Therapeutic Molecules. ACS Appl Mater Interfaces [Epub ahead of print]. [abstract]

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