Real-Time Dissection of the Transportation and miRNA-Release Dynamics of Small Extracellular Vesicles

Adv Sci (Weinh). 2023 Mar;10(7):e2205566. doi: 10.1002/advs.202205566. Epub 2023 Jan 4.

Abstract

Extracellular vesicles (EVs) are cell-derived membrane-enclosed structures that deliver biomolecules for intercellular communication. Developing visualization methods to elucidate the spatiotemporal dynamics of EVs' behaviors will facilitate their understanding and translation. With a quantum dot (QD) labeling strategy, a single particle tracking (SPT) platform is proposed here for dissecting the dynamic behaviors of EVs. The interplays between tumor cell-derived small EVs (T-sEVs) and endothelial cells (ECs) are specifically investigated based on this platform. It is revealed that, following a clathrin-mediated endocytosis by ECs, T-sEVs are transported to the perinuclear region in a typical three-stage pattern. Importantly, T-sEVs frequently interact with and finally enter lysosomes, followed by quick release of their carried miRNAs. This study, for the first time, reports the entire process and detailed dynamics of T-sEV transportation and cargo-release in ECs, leading to better understanding of their proangiogenic functions. Additionally, the QD-based SPT technique will help uncover more secrets of sEV-mediated cell-cell communication.

Keywords: angiogenesis; extracellular vesicles; miRNA; quantum dots; single particle tracking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication
  • Endocytosis
  • Endothelial Cells
  • Extracellular Vesicles* / chemistry
  • MicroRNAs* / analysis

Substances

  • MicroRNAs