Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo

Sezin Aday, Inbal Hazan-Halevy, Aranzazu Chamorro-Jorganes, Maryam Anwar, Meir Goldsmith, Nicholas Beazley-Long, Susmita Sahoo, Navneet Dogra, Walid Sweaad, Francesco Catapano, Sho Ozaki-Tan, Gianni D. Angelini, Paolo Madeddu, Andrew V. Benest, Dan Peer, Costanza Emanueli

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name “exosomes”) with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired “artificial exosomes” (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34+ cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.

Original languageEnglish
Pages (from-to)2239-2252
Number of pages14
JournalMolecular Therapy
Volume29
Issue number7
DOIs
StatePublished - 7 Jul 2021

Keywords

  • angiogenesis
  • endothelial cells
  • extracellular vesicles
  • let-7b-5p
  • microRNAs
  • nanomedicine

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo'. Together they form a unique fingerprint.

Cite this