Measurement and Standardization Challenges for Extracellular Vesicle Therapeutic Delivery Vectors

Overview

Journal Nanomedicine (Lond)

Specialty Biotechnology

Date 2020 Sep 5

PMID 32885720

Citations 11

Authors

Bryant C Nelson

Samantha Maragh

Ionita C Ghiran

Jennifer C Jones

Paul C DeRose

Elzafir Elsheikh

Wyatt N Vreeland

Lili Wang

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs), such as exosomes and microvesicles, are nonreplicating lipid bilayer particles shed by most cell types which have the potential to revolutionize the development and efficient delivery of clinical therapeutics. This article provides an introduction to the landscape of EV-based vectors under development for the delivery of protein- and nucleic acid-based therapeutics. We highlight some of the most pressing measurement and standardization challenges that limit the translation of EVs to the clinic. Current challenges limiting development of EVs for drug delivery are the lack of: standardized cell-based platforms for the production of EV-based therapeutics; EV reference materials that allow researchers/manufacturers to validate EV measurements and standardized measurement systems for determining the molecular composition of EVs.

Citing Articles

Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia.

Ravi Mythili V, Rajendran R, Arun R, Loganathbabu V, Reyaz D, Nagarajan A Bioengineering (Basel). 2025; 12(1).

PMID: 39851366 PMC: 11762151. DOI: 10.3390/bioengineering12010092.

Corneal Treatment, Repair, and Regeneration: Exosomes at Rescue.

Robbins B, Montreuil K, Kundu N, Kumar P, Agrahari V Pharmaceutics. 2024; 16(11).

PMID: 39598547 PMC: 11597686. DOI: 10.3390/pharmaceutics16111424.

Nanoparticle Tracking Analysis: An Effective Tool to Characterize Extracellular Vesicles.

Kowkabany G, Bao Y Molecules. 2024; 29(19).

PMID: 39407601 PMC: 11477862. DOI: 10.3390/molecules29194672.

Potential Therapeutic Application and Mechanism of Action of Stem Cell-Derived Extracellular Vesicles (EVs) in Systemic Lupus Erythematosus (SLE).

Rajeev Kumar S, Sakthiswary R, Lokanathan Y Int J Mol Sci. 2024; 25(4).

PMID: 38397121 PMC: 10889333. DOI: 10.3390/ijms25042444.

Preparation of Nanoparticle-Loaded Extracellular Vesicles Using Direct Flow Filtration.

Mansur S, Habib S, Hawkins M, Brown S, Weinman S, Bao Y Pharmaceutics. 2023; 15(5).

PMID: 37242792 PMC: 10221999. DOI: 10.3390/pharmaceutics15051551.

References

Murphy D, de Jong O, Brouwer M, Wood M, Lavieu G, Schiffelers R . Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking. Exp Mol Med. 2019; 51(3):1-12. PMC: 6418170. DOI: 10.1038/s12276-019-0223-5. View

Dubochet J . Cryo-EM--the first thirty years. J Microsc. 2012; 245(3):221-4. DOI: 10.1111/j.1365-2818.2011.03569.x. View

Kulp A, Kuehn M . Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol. 2010; 64:163-84. PMC: 3525469. DOI: 10.1146/annurev.micro.091208.073413. View

Yamashita T, Takahashi Y, Takakura Y . Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application. Biol Pharm Bull. 2018; 41(6):835-842. DOI: 10.1248/bpb.b18-00133. View

El Andaloussi S, Mager I, Breakefield X, Wood M . Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013; 12(5):347-57. DOI: 10.1038/nrd3978. View

Sims C, Hanna S, Heller D, Horoszko C, Johnson M, Montoro Bustos A . Redox-active nanomaterials for nanomedicine applications. Nanoscale. 2017; 9(40):15226-15251. PMC: 5648636. DOI: 10.1039/c7nr05429g. View

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

Zhang Y, Liu Y, Liu H, Tang W . Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019; 9:19. PMC: 6377728. DOI: 10.1186/s13578-019-0282-2. View

Mittereder N, March K, Trapnell B . Evaluation of the concentration and bioactivity of adenovirus vectors for gene therapy. J Virol. 1996; 70(11):7498-509. PMC: 190817. DOI: 10.1128/JVI.70.11.7498-7509.1996. View

10.

de Oliveira Jr G, Zigon E, Rogers G, Davodian D, Lu S, Jovanovic-Talisman T . Detection of Extracellular Vesicle RNA Using Molecular Beacons. iScience. 2020; 23(1):100782. PMC: 6992906. DOI: 10.1016/j.isci.2019.100782. View

11.

Whisner C, Aktipis C . The Role of the Microbiome in Cancer Initiation and Progression: How Microbes and Cancer Cells Utilize Excess Energy and Promote One Another's Growth. Curr Nutr Rep. 2019; 8(1):42-51. PMC: 6426824. DOI: 10.1007/s13668-019-0257-2. View

12.

van der Pol E, Boing A, Gool E, Nieuwland R . Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles. J Thromb Haemost. 2015; 14(1):48-56. DOI: 10.1111/jth.13190. View

13.

Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M . Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res. 2009; 7(12):5157-66. PMC: 2696236. DOI: 10.1021/pr8004887. View

14.

Lamichhane T, Raiker R, Jay S . Exogenous DNA Loading into Extracellular Vesicles via Electroporation is Size-Dependent and Enables Limited Gene Delivery. Mol Pharm. 2015; 12(10):3650-7. PMC: 4826735. DOI: 10.1021/acs.molpharmaceut.5b00364. View

15.

Thery C, Zitvogel L, Amigorena S . Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002; 2(8):569-79. DOI: 10.1038/nri855. View

16.

Margolis L, Sadovsky Y . The biology of extracellular vesicles: The known unknowns. PLoS Biol. 2019; 17(7):e3000363. PMC: 6667152. DOI: 10.1371/journal.pbio.3000363. View

17.

Jeong K, Yu Y, You J, Rhee W, Kim J . Exosome-mediated microRNA-497 delivery for anti-cancer therapy in a microfluidic 3D lung cancer model. Lab Chip. 2020; 20(3):548-557. DOI: 10.1039/c9lc00958b. View

18.

Malhotra H, Sheokand N, Kumar S, Chauhan A, Kumar M, Jakhar P . Exosomes: Tunable Nano Vehicles for Macromolecular Delivery of Transferrin and Lactoferrin to Specific Intracellular Compartment. J Biomed Nanotechnol. 2016; 12(5):1101-14. DOI: 10.1166/jbn.2016.2229. View

19.

Bellavia D, Raimondo S, Calabrese G, Forte S, Cristaldi M, Patinella A . Interleukin 3- receptor targeted exosomes inhibit and Chronic Myelogenous Leukemia cell growth. Theranostics. 2017; 7(5):1333-1345. PMC: 5399597. DOI: 10.7150/thno.17092. View

20.

Ferguson S, Nguyen J . Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity. J Control Release. 2016; 228:179-190. DOI: 10.1016/j.jconrel.2016.02.037. View