Pulsed Focal Ultrasound as a Non-Invasive Method to Deliver Exosomes in the Brain/Stroke

Ahmet Alptekin, Mohammad B. Khan, Roxan Ara, Mohammad H. Rashid, Fengchong Kong, Mahrima Parvin, Joseph A. Frank, Rajiv Chopra, Krishnan Dhandapani, Ali S. Arbab

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Exosomes, a component of extracellular vesicles, are shown to carry important small RNAs, mRNAs, protein, and bioactive lipid from parent cells and are found in most biological fluids. Investigators have demonstrated the importance of mesenchymal stem cells derived exosomes in repairing stroke lesions. However, exosomes from endothelial progenitor cells have not been tested in any stroke model, nor has there been an evaluation of whether these exosomes target/home to areas of pathology. Targeted delivery of intravenous administered exosomes has been a great challenge, and a targeted delivery system is lacking to deliver naïve (unmodified) exosomes from endothelial progenitor cells to the site of interest. Pulsed focused ultrasound is being used for therapeutic and experimental purposes. There has not been any report showing the use of low-intensity pulsed focused ultrasound to deliver exosomes to the site of interest in stroke models. In this proof of principle study, we have shown different parameters of pulsed focused ultrasound to deliver exosomes in the intact and stroke brain with or without intravenous administration of nanobubbles. The study results showed that administration of nanobubbles is detrimental to the brain structures (micro bleeding and white matter destruction) at peak negative pressure of >0.25 megapascal, despite enhanced delivery of intravenous administered exosomes. However, without nanobubbles, pulsed focused ultrasound enhances the delivery of exosomes in the stroke area without altering the brain structures.

Original languageEnglish (US)
Pages (from-to)1170-1183
Number of pages14
JournalJournal of Biomedical Nanotechnology
Volume17
Issue number6
DOIs
StatePublished - Jun 1 2021

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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