Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

Abstract

Since the 2013 Nobel Prize was awarded for the discovery of vesicle trafficking, a subgroup of nanovesicles called exosomes has been driving the research field to a new regime for understanding cellular communication. This exosome-dominated traffic control system has increased understanding of many diseases, including cancer metastasis, diabetes, and HIV. In addition to the important diagnostic role, exosomes are particularly attractive for drug delivery, due to their distinctive properties in cellular information transfer and uptake. Compared to viral and non-viral synthetic systems, the natural, cell-derived exosomes exhibit intrinsic payload and bioavailability. Most importantly, exosomes easily cross biological barriers, obstacles that continue to challenge other drug delivery nanoparticle systems. Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood–brain barrier (BBB), blood–cerebrospinal fluid barrier (BCSFB), blood–lymph barrier (BlyB), blood–air barrier (BAB), stromal barrier (SB), blood–labyrinth barrier (BLaB), blood–retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform. However, the systematic reviews summarizing such discoveries are still limited. This review covers state-of-the-art exosome research on crossing several important biological barriers with a focus on the current, accepted models used to explain the mechanisms of barrier crossing, including tight junctions. The potential to design and engineer exosomes to enhance delivery efficacy, leading to future applications in precision medicine and immunotherapy, is discussed.

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

“…They can also cross various biological fluids and pass through plasma membranes, thus delivering therapeutic compounds into the cytoplasm of target cells [147]. Therefore, exosomes have high potential as delivery vehicles of therapeutic agents, particularly because they can also cross the blood-brain barrier [168,169]. Compared with other drug carriers, due to the abovementioned properties, they have a greater potential to be used for biomedical purposes, especially in the treatment of more difficult to treat diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases [139].…”

Molecular Mechanisms of Drug Resistance in Glioblastoma

“…The invasive approaches include intrathecal administration by the direct administration or catheters [25], convention-enhanced delivery via bulk flow [26], interstitial wafers, and implants [27]. The non-invasive approaches suggest the usage of chemical modification of drugs such as lipidization [28], substrates for carrier-mediated transcytosis [29], substrates for receptor-mediated transcytosis, virus-mediated bloodbrain barrier delivery [30,31], and exosome-mediated blood-brain barrier delivery [32]. There are also several methods different from the above two approaches: the intranasal delivery route [33], the modulation of the blood-brain barrier permeability by hyperosmotic agents [34], and the use of focused ultrasound [35].…”

Extracellular Vesicles as Promising Carriers in Drug Delivery: Considerations from a Cell Biologist’s Perspective

“…Thanks to their biological proprieties EVs represent a promising carrier for drug delivery. Indeed, using EVs as “drug carriers” provides several advantages, such us: low immunological response [ 48 ]; targeting potential [ 49 ]; easy bypass of cellular barriers [ 50 ]; cargo protection [ 51 ]. …”