Potential Use of Exosomes as Diagnostic Biomarkers and in Targeted Drug Delivery: Progress in Clinical and Preclinical Applications

Abstract

Exosomes are cell-derived vesicles containing heterogeneous active biomolecules such as proteins, lipids, mRNAs, receptors, immune regulatory molecules, and nucleic acids. They typically range in size from 30 to 150 nm in diameter. An exosome’s surfaces can be bioengineered with antibodies, fluorescent dye, peptides, and tailored for small molecule and large active biologics. Exosomes have enormous potential as a drug delivery vehicle due to enhanced biocompatibility, excellent payload capability, and reduced immunogenicity compared to alternative polymeric-based carriers. Because of active targeting and specificity, exosomes are capable of delivering their cargo to exosome-recipient cells. Additionally, exosomes can potentially act as early stage disease diagnostic tools as the exosome carries various protein biomarkers associated with a specific disease. In this review, we summarize recent progress on exosome composition, biological characterization, and isolation techniques. Finally, we outline the exosome’s clinical applications and preclinical advancement to provide an outlook on the importance of exosomes for use in targeted drug delivery, biomarker study, and vaccine development.

Exosomes, a New Star for Targeted Delivery

“…Simple incubation with surfactants like saponin or triton can increase the membrane permeability of exosomes and facilitate cargo loading, among which saponin is the most widely used surfactant in this field (Huda et al, 2021). As a natural surfactant, saponin interacts with the membrane-bound cholesterol, which creates pores and increases the permeability of cell/exosome membranes (Jamur and Oliver, 2010).…”

Exosomes as Smart Nanoplatforms for Diagnosis and Therapy of Cancer

“…Until January 2021, there were 205 clinical trials related to exosome research. Of the 205 trials, around 87 trials involved cancer-related studies (179). Among these clinical trials, exosomebased phase I and II clinical trials have been completed in advanced lung cancer patients showing promising data (148).…”

Emerging Nano-Carrier Strategies for Brain Tumor Drug Delivery and Considerations for Clinical Translation

“…Studies have shown that exosomes from endothelial cells interact with the BBB, whereas exosomes from cultured GBM cells could not. However, hypoxic GBM cells produced exosomes capable of modulating BBB permeability [127]. Cancer cells also produce exosomes which weaken the BBB, which may be a way to pre-condition the brain for metastasis [128].…”

“…Since some exosomes can cross the BBB, they may be used as delivery vehicles for conventional chemotherapeutic drugs. Drugs may be loaded into exosomes by a variety of methods including simple incubation and passive uptake, sonication, electroporation, freeze-thaw or use of surfactants [127]. A study by Yang and colleagues showed that bEND.3-derived exosomes could be loaded with doxorubicin and paclitaxel (7.3 ng and 132.9 ng of drug per 1 µg exosome) and showed better therapeutic efficacy than free drug in a zebrafish tumor model [131].…”