Towards analyzing the potential of exosomes to deliver microRNA therapeutics

J Cell Physiol. 2021 Feb;236(2):1529-1544. doi: 10.1002/jcp.29991. Epub 2020 Aug 4.

Abstract

Exosome selectivity mechanisms underlying exosome-target cell interactions and the specific traits affecting their capability to communicate still remain unclear. Moreover, the capacity of exosomes to efficiently deliver their molecular cargos intracellularly needs precise investigation towards establishing functional exosome-based delivery platforms exploitable in the clinical practice. The current study focuses on: (a) exosome production from normal MRC-5 and Vero cells growing in culture, (b) physicochemical characterization by dynamic light scattering (DLS) and cryo-transmission electron microscopy; (c) cellular uptake studies of rhodamine-labeled exosomes in normal and cancer cells, providing to exosomes either "autologous" or "heterologous" cellular delivery environments; and (d) loading exogenous Alexa Fluor 488-labeled siRNA into exosomes for the assessment of their delivering capacity by immunofluorescence in a panel of recipient cells. The data obtained thus far indicate that MRC-5 and Vero exosomes, indeed exhibit an interesting delivering profile, as promising "bio-shuttles," being pharmacologically exploitable in the context of theranostic applications.

Keywords: cellular uptake selectivity; cryo-transmission electron microscopy; delivery; exosomes; siRNAs/microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / genetics
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cryoelectron Microscopy
  • Drug Delivery Systems*
  • Exosomes / chemistry*
  • Exosomes / genetics
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / therapeutic use*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / therapeutic use*
  • Vero Cells

Substances

  • MicroRNAs
  • RNA, Small Interfering