Insights into Exosome Transport through the Blood–Brain Barrier and the Potential Therapeutical Applications in Brain Diseases

Abstract

Drug delivery to the central nervous system (CNS) is limited due to the presence of the blood–brain barrier (BBB), a selective physiological barrier located at the brain microvessels that regulates the flow of cells, molecules and ions between the blood and the brain. Exosomes are nanosized extracellular vesicles expressed by all cell types and that function as cargos, allowing for communication between the cells. The exosomes were shown to cross or regulate the BBB in healthy and disease conditions. However, the mechanistic pathways by which exosomes cross the BBB have not been fully elucidated yet. In this review, we explore the transport mechanisms of exosomes through the BBB. A large body of evidence suggests that exosome transport through the BBB occurs primarily through transcytosis. The transcytosis mechanisms are influenced by several regulators. Inflammation and metastasis also enhance exosome trafficking across the BBB. We also shed light on the therapeutical applications of exosomes for treating brain diseases. Further investigations are essential to provide clearer insights related to trafficking of exosomes across the BBB and disease treatment.

Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases

“…Further, they can carry cargo, such as iron particles in this study and others 26,28,30,33,34,96,97 , as well as therapeutics 19,20,22–25,27,94,95 . The mechanisms in which EVs cross the BBB is not fully understood; however, some possible routes which have been explored are micropinocytosis, clathrin-dependent endocytosis and caveolae-dependent endocytosis 17,18,98,99 .…”

Research Advances of Engineered Exosomes as Drug Delivery Carrier

“…Engineered exosomes have excellent efficacy in the therapy of neurodegenerative diseases, brain cancer, and encephalitis due to the advantages of high targeting and efficient drug delivery. − Engineered exosomes have been shown to be involved in mediating several physiological processes required for normal brain function . Compared with other therapeutic drug delivery systems, engineered exosomes have immunomodulatory effects, strong targeting of lesion sites, and blood-brain penetration . Moreover, the engineered exosomes are modified to reduce their distribution in the liver and spleen, and more effectively target to the brain tissue, which is a promising new approach for the treatment of brain diseases .…”

“…145 Compared with other therapeutic drug delivery systems, engineered exosomes have immunomodulatory effects, strong targeting of lesion sites, and blood-brain penetration. 146 Moreover, the engineered exosomes are modified to reduce their distribution in the liver and spleen, and more effectively target to the brain tissue, which is a promising new approach for the treatment of brain diseases. 147 For instance, Yu et al have proved that blood-derived exosomes have natural brain-targeting capabilities.…”

Progress and Challenges in the Diagnosis and Treatment of Brain Cancer Using Nanotechnology

“…Initially, it was believed that EVs were garbage sacks secreted by cells as a self-cleaning mechanism. 197 As research proceeded, EVs were revealed to stably transport signal molecules like proteins, mRNAs, miRNAs, and lipids for intercellular communication, illness detection, development, and treatment. 198 Due to their unique structure, EVs can be modified to load specific proteins, genetic lipids, genetic materials, and genomic DNA (gDNA) from their progenitor cell.…”

“…These vesicles are abundantly found in body fluids. Initially, it was believed that EVs were garbage sacks secreted by cells as a self-cleaning mechanism . As research proceeded, EVs were revealed to stably transport signal molecules like proteins, mRNAs, miRNAs, and lipids for intercellular communication, illness detection, development, and treatment .…”