Pulsed Focal ultrasound as a non-invasive method to deliver exosomes in the brain/stroke

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 (MSCs) derived exosomes in repairing stroke lesions. However, exosomes from endothelial progenitor cells (EPCs) 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 IV administered exosomes has been a great challenge and a targeted delivery system is lacking to deliver naive (unmodified) exosomes from EPCs to the site of interest. Pulsed focused ultrasound (pFUS) is being used for therapeutic and experimental purposes. There has not been any report showing the use of pulsed low-intensity pFUS to deliver exosomes to the site of interest in models of stroke. In this proof of principle study, we have shown different parameters of pFUS to deliver exosomes in the intact and stroke brain with or without IV 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 (PNP) of >0.25 MPa, despite enhanced delivery of IV administered exosomes. However, without nanobubbles, pFUS PNP = 1 to 2 MPa enhances the delivery of exosomes in the stroke area without altering the brain structures.

Rat Bone Mesenchymal Stem Cell‐Derived Exosomes Loaded with miR‐494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury

“…Exosomes are closely related to the occurrence, progress, and recovery of central nervous system injury [ 8 – 10 ]. After spinal cord injury, exosomes can regulate the autonomic regeneration function of neurons and, also, affect the remyelination of the spinal cord, the metabolic activity, and inflammatory environment around the lesions.…”

Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications

“…After washing with phosphate-buffered saline (PBS), the drug-loaded exosome suspension is centrifuged again for 70 minutes and resuspended in an appropriate volume of PBS to obtain the drug-loaded exosome. With the wide application of this technology, Alptekin et al 30 demonstrated an enhanced drug delivery of exosomes treated with ultrasound, and those exosomes can successfully transport the drugs to the stroke area of the brain without harming the normal brain structure.…”