Title

Exosome-mediated delivery of functionally active miRNA-155 inhibitor to macrophages

UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Date

3-29-2014

Document Type

Article

Disciplines

Cell Biology | Digestive System Diseases | Gastroenterology | Genomics | Hepatology | Immunopathology | Nanomedicine

Abstract

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically significant reduction in LPS-induced TNFalpha production and partially prevented LPS-induced decrease in SOCS1 mRNA levels. Furthermore, exosome-mediated miRNA-155 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo.

Rights and Permissions

Citation: Nanomedicine. 2014 Mar 29. doi: 10.1016/j.nano.2014.03.014 Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

24685946