Clinical EV Research
Although research on EVs has been progressing at a rapid rate since their discovery several decades ago, further investigations are needed to develop a complete understanding of their functional capabilities.
EVs are involved in an array of physiological and pathological processes including stem cell differentiation, inflammation, tumorigenesis, blood coagulation, and many more.(1)
As a result, their ability to act as carriers of biomarkers for diseases has become a prominent and rewarding topic of scientific discovery. The use of EVs as biomarkers is particularly convenient because these cargo vehicles are present in most human biological fluids and can be extracted using minimally or non-invasive “liquid biopsy” methods.
Additionally, a growing body of evidence points to the comparability of cell culture-derived EVs and patient-derived EVs for similar diagnoses.(2-5) Cells harvested from patients with a particular disease appear to maintain their EV profile over time, consistently releasing EVs of the same composition. The EV profiles of several disease phenotypes have been characterized,(6-11) allowing the extrapolation from cell culture-derived EVs to liquid biopsy-derived EVs, further enabling the use of fluid samples as diagnostic tests for biomarkers of disease.
The utility of EVs for diagnostic purposes is not limited to identifying a disease state, but also for assessing the efficacy of a therapeutics and other clinical treatments.
Why EVs hold promise as drug delivery vehicles
- EVs possess many inherent advantages that make them ideal candidates for the development of drug delivery systems:
- EVs are intrinsically capable of delivering an array of therapeutic cargo including nucleic acids and proteins.
- EVs appear to be equipped to overcome biological barriers, such as the blood brain barrier, to preferentially target particular cell types and tissues.(12, 13)
- The lipid bilayer and negatively charged surface of EVs under physiological conditions give them excellent circulatory stability.(14, 15)
- Unlike synthetic drug delivery molecules, EVs are produced and packaged by endogenous cellular machinery. Thus, EVs have the potential to significantly simplify the drug loading process, which currently represents a major challenge in developing novel delivery systems. (16, 17)
- EV safety profiles are quite encouraging. Owing to their endogenous nature, EVs are less likely to be immunogenic or cytotoxic than other synthetic delivery systems. Moreover, EVs are nonreplicative and nonmutagenic, which gives them an edge over some virus-based delivery particles.
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- Ipas H, Guttin A, Issartel JP. Exosomal MicroRNAs in Tumoral U87 MG Versus Normal Astrocyte Cells. Microrna. 2015;4(2):131-45.
- Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470-6.
- Akers JC, Ramakrishnan V, Kim R, Phillips S, Kaimal V, Mao Y, et al. miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients. J Neurooncol. 2015;123(2):205-16.
- Bellingham SA, Coleman BM, Hill AF. Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res. 2012;40(21):10937-49.
- Belov L, Matic KJ, Hallal S, Best OG, Mulligan SP, Christopherson RI. Extensive surface protein profiles of extracellular vesicles from cancer cells may provide diagnostic signatures from blood samples. J Extracell Vesicles. 2016;5:25355.
- Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One. 2014;9(4):e92921.
- Taylor DD, Gercel-Taylor C. Exosome platform for diagnosis and monitoring of traumatic brain injury. Philos Trans R Soc Lond B Biol Sci. 2014;369(1652).
- Xiao D, Ohlendorf J, Chen Y, Taylor DD, Rai SN, Waigel S, et al. Identifying mRNA, microRNA and protein profiles of melanoma exosomes. PLoS One. 2012;7(10):e46874.
- Zhong S, Chen X, Wang D, Zhang X, Shen H, Yang S, et al. MicroRNA expression profiles of drug-resistance breast cancer cells and their exosomes. Oncotarget. 2016;7(15):19601-9.
- Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release. 2015;207:18-30.
- Lai RC, Yeo RW, Tan KH, Lim SK. Exosomes for drug delivery - a novel application for the mesenchymal stem cell. Biotechnol Adv. 2013;31(5):543-51.
- Liu Y, Yang G, Jin S, Xu L, Zhao CX. Development of High-Drug-Loading Nanoparticles. Chempluschem. 2020;85(9):2143-57.
- Bunggulawa EJ, Wang W, Yin T, Wang N, Durkan C, Wang Y, et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnology. 2018;16(1):81.
- Kaddour H, Panzner TD, Welch JL, Shouman N, Mohan M, Stapleton JT, et al. Electrostatic Surface Properties of Blood and Semen Extracellular Vesicles: Implications of Sialylation and HIV-Induced Changes on EV Internalization. Viruses. 2020;12(10).
- Midekessa G, Godakumara K, Ord J, Viil J, Lattekivi F, Dissanayake K, et al. Zeta Potential of Extracellular Vesicles: Toward Understanding the Attributes that Determine Colloidal Stability. ACS Omega. 2020;5(27):16701-10.