Extracellular Vesicles As Tools and Targets in Therapy for Diseases

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2024 Feb 4

PMID 38311623

Authors

Mudasir A Kumar

Sadaf K Baba

Hana Q Sadida

Sara Al Marzooqi

Jayakumar Jerobin

Faisal H Altemani

Naseh Algehainy

Mohammad A Alanazi

Abdul-Badi Abou-Samra

Rakesh Kumar

Ammira S Al-Shabeeb Akil

Muzafar A Macha

Rashid Mir

Ajaz A Bhat

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and are ubiquitously released from cells under normal and pathological conditions. Human serum is a rich source of these EVs, though their isolation from serum proteins and non-EV lipid particles poses challenges. These vesicles transport various cellular components such as proteins, mRNAs, miRNAs, DNA, and lipids across distances, influencing numerous physiological and pathological events, including those within the tumor microenvironment (TME). Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents, drug delivery systems, and disease biomarkers. Especially in cancer diagnostics, EV detection can pave the way for early identification and offers potential as diagnostic biomarkers. Moreover, various EV subtypes are emerging as targeted drug delivery tools, highlighting their potential clinical significance. The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled. Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future. In this review, we discuss in detail the roles of EVs across various conditions, including cancers (encompassing head and neck, lung, gastric, breast, and hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune and renal diseases, emphasizing the potential advancements in molecular diagnostics and drug delivery.

Citing Articles

Targeting Neuroinflammation in Preterm White Matter Injury: Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes.

Zhang X, Zhang Y, Peng X, Yang L, Miao J, Yue Y Cell Mol Neurobiol. 2025; 45(1):23.

PMID: 40072734 PMC: 11903990. DOI: 10.1007/s10571-025-01540-6.

Gene therapy and genome-editing for schwannoma in NF2-related schwannomatosis: current understanding and future directions.

Tamura R, Yo M, Toda M J Neurooncol. 2025; .

PMID: 40055258 DOI: 10.1007/s11060-025-04995-1.

Emerging Frontiers in acute kidney injury: The role of extracellular vesicles.

Li S, Zhou L, Huang Y, Tang S Bioact Mater. 2025; 48:149-170.

PMID: 40046015 PMC: 11880721. DOI: 10.1016/j.bioactmat.2025.02.018.

Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.

Balaraman A, Babu M, Afzal M, Sanghvi G, M M R, Gupta S Regen Ther. 2025; 28:558-572.

PMID: 40034540 PMC: 11872554. DOI: 10.1016/j.reth.2025.01.019.

CircRNAs in Colorectal Cancer: Unveiling Their Roles and Exploring Therapeutic Potential.

Ding Y, Song X, Chen J Biochem Genet. 2025; .

PMID: 40029586 DOI: 10.1007/s10528-025-11068-5.

References

Alberro A, Iparraguirre L, Fernandes A, Otaegui D . Extracellular Vesicles in Blood: Sources, Effects, and Applications. Int J Mol Sci. 2021; 22(15). PMC: 8347110. DOI: 10.3390/ijms22158163. View

Marcoux G, Magron A, Sut C, Laroche A, Laradi S, Hamzeh-Cognasse H . Platelet-derived extracellular vesicles convey mitochondrial DAMPs in platelet concentrates and their levels are associated with adverse reactions. Transfusion. 2019; 59(7):2403-2414. DOI: 10.1111/trf.15300. View

Shen R, Wang Y, Wang C, Yin M, Liu H, Chen J . MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. Am J Transl Res. 2015; 7(10):2115-26. PMC: 4656789. View

Kim O, Hwangbo C, Tran P, Lee J . Syntenin-1-mediated small extracellular vesicles promotes cell growth, migration, and angiogenesis by increasing onco-miRNAs secretion in lung cancer cells. Cell Death Dis. 2022; 13(2):122. PMC: 8826407. DOI: 10.1038/s41419-022-04594-2. View

Brett S, Lucien F, Guo C, Williams K, Kim Y, Durfee P . Immunoaffinity based methods are superior to kits for purification of prostate derived extracellular vesicles from plasma samples. Prostate. 2017; 77(13):1335-1343. DOI: 10.1002/pros.23393. View

Ghosh A, Davey M, Chute I, Griffiths S, Lewis S, Chacko S . Rapid isolation of extracellular vesicles from cell culture and biological fluids using a synthetic peptide with specific affinity for heat shock proteins. PLoS One. 2014; 9(10):e110443. PMC: 4201556. DOI: 10.1371/journal.pone.0110443. View

Fang S, Tian H, Li X, Jin D, Li X, Kong J . Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification. PLoS One. 2017; 12(4):e0175050. PMC: 5378374. DOI: 10.1371/journal.pone.0175050. View

Mendt M, Kamerkar S, Sugimoto H, McAndrews K, Wu C, Gagea M . Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. 2018; 3(8). PMC: 5931131. DOI: 10.1172/jci.insight.99263. View

Lu J, Li P, Du X, Liu Y, Zhang B, Qi F . Regulatory T cells induce transplant immune tolerance. Transpl Immunol. 2021; 67:101411. DOI: 10.1016/j.trim.2021.101411. View

10.

Albino D, Falcione M, Uboldi V, Temilola D, Sandrini G, Merulla J . Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer. Commun Biol. 2021; 4(1):119. PMC: 7838273. DOI: 10.1038/s42003-020-01642-5. View

11.

Shi X, Cheng Q, Hou T, Han M, Smbatyan G, Lang J . Genetically Engineered Cell-Derived Nanoparticles for Targeted Breast Cancer Immunotherapy. Mol Ther. 2019; 28(2):536-547. PMC: 7001084. DOI: 10.1016/j.ymthe.2019.11.020. View

12.

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

13.

Forder A, Hsing C, Trejo Vazquez J, Garnis C . Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis. Cells. 2021; 10(12). PMC: 8700460. DOI: 10.3390/cells10123429. View

14.

Yap S, Tan K, Abd Rahaman N, Hamid N, Ooi D, Tor Y . Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorated Insulin Resistance in Type 2 Diabetes Mellitus Rats. Pharmaceutics. 2022; 14(3). PMC: 8948940. DOI: 10.3390/pharmaceutics14030649. View

15.

OReilly D, Dorodnykh D, Avdeenko N, Nekliudov N, Garssen J, Elolimy A . Perspective: The Role of Human Breast-Milk Extracellular Vesicles in Child Health and Disease. Adv Nutr. 2020; 12(1):59-70. PMC: 7849950. DOI: 10.1093/advances/nmaa094. View

16.

Maus R, Jakub J, Nevala W, Christensen T, Noble-Orcutt K, Sachs Z . Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation. Front Immunol. 2017; 8:358. PMC: 5372822. DOI: 10.3389/fimmu.2017.00358. View

17.

Yang Y, Li C, Chan L, Wei Y, Hsu J, Xia W . Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res. 2018; 28(8):862-864. PMC: 6082826. DOI: 10.1038/s41422-018-0060-4. View

18.

Siljander P, Carpen O, Lassila R . Platelet-derived microparticles associate with fibrin during thrombosis. Blood. 1996; 87(11):4651-63. View

19.

Dar G, Mendes C, Kuan W, Speciale A, Conceicao M, Gorgens A . GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain. Nat Commun. 2021; 12(1):6666. PMC: 8602309. DOI: 10.1038/s41467-021-27056-3. View

20.

Sanwlani R, Gangoda L . Role of Extracellular Vesicles in Cell Death and Inflammation. Cells. 2021; 10(10). PMC: 8534608. DOI: 10.3390/cells10102663. View