Applications of Exosomes in Cancer Therapy
DOI:
https://doi.org/10.58445/rars.858Keywords:
Exosomes, Cancer Therapy, Drug Delivery, BiomarkersAbstract
This systematic review explores the field of utilizing exosomes for cancer therapy, providing a comprehensive analysis of their mechanisms, applications, advantages, and limitations. Exosomes, specialized extracellular vesicles, demonstrate promising attributes as potential vehicles for drug delivery due to their inherent biocompatibility, immunotolerance, and ability to traverse biological barriers. The review categorizes exosomes based on their in vivo sources, including milk, dendritic cells, mesenchymal stem cells, erythrocytes, and tumor cells, elucidating the unique advantages and challenges associated with each type. Additionally, the study delves into various exosome-loading techniques such as transfection, incubation, and electroporation. The clinical implications of exosomes as cancer biomarkers are detailed, including their role in early detection and diagnosis through exosomal RNA and protein analysis. Despite the promising potential, the review also highlights existing challenges in industrial-scale production, standardization, and long-term biosafety. Finally, the paper outlines future research directions aimed at refining exosome-based therapies, addressing existing limitations, and realizing their full therapeutic potential against cancer.
References
Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and Biomedical Applications of Exosomes. Science, 367(6478). https://doi.org/10.1126/science.aau6977
Yue, B., Yang, H., Wang, J., Ru, W., Wu, J., Huang, Y., Lan, X., Lei, C., & Chen, H. (2020). Exosome biogenesis, secretion and function of exosomal miRNAs in skeletal muscle myogenesis. Cell Proliferation, 53(7). https://doi.org/10.1111/cpr.12857
Li, J., Huang, Y., Sun, H., & Yang, L. (2023). Mechanism of mesenchymal stem cells and exosomes in the treatment of age-related diseases. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1181308
Chen, L., Wang, L., Zhu, L., Xu, Z., Liu, Y., Li, Z., Zhou, J., & Luo, F. (2022). Exosomes as Drug Carriers in Anti-Cancer Therapy. Frontiers in Cell and Developmental Biology, 10, 728616. https://doi.org/10.3389/fcell.2022.728616
Zhang, L., & Yu, D. (2019). Exosomes in cancer development, metastasis, and immunity. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1871(2), 455–468. https://doi.org/10.1016/j.bbcan.2019.04.004
Reif, S., Elbaum Shiff, Y., & Golan-Gerstl, R. (2019). Milk-derived exosomes (MDEs) have a different biological effect on normal fetal colon epithelial cells compared to colon tumor cells in a miRNA-dependent manner. Journal of Translational Medicine, 17(1). https://doi.org/10.1186/s12967-019-2072-3
Zeng, H., Guo, S., Ren, X., Wu, Z., Liu, S., & Yao, X. (2023). Current Strategies for Exosome Cargo Loading and Targeting Delivery. 12(10), 1416–1416. https://doi.org/10.3390/cells12101416
Feng, X., Chen, X., Zheng, X., Zhu, H., Qi, Q., Liu, S., Zhang, H., & Che, J. (2021). Latest Trend of Milk Derived Exosomes: Cargos, Functions, and Applications. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.747294
Vashisht, M., Rani, P., Onteru, S. K., & Singh, D. (2017). Curcumin Encapsulated in Milk Exosomes Resists Human Digestion and Possesses Enhanced Intestinal Permeability in Vitro. Applied Biochemistry and Biotechnology, 183(3), 993–1007. https://doi.org/10.1007/s12010-017-2478-4
Liu, K. (2016). Dendritic Cells. Encyclopedia of Cell Biology, 741–749. https://doi.org/10.1016/B978-0-12-394447-4.30111-0
Pitt, J. M., Charrier, M., Viaud, S., André, F., Besse, B., Chaput, N., & Zitvogel, L. (2014). Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. Journal of Immunology (Baltimore, Md.: 1950), 193(3), 1006–1011. https://doi.org/10.4049/jimmunol.1400703
Théry, C., Regnault, A., Garin, J., Wolfers, J., Zitvogel, L., Ricciardi-Castagnoli, P., Raposo, G., & Amigorena, S. (1999). Molecular Characterization of Dendritic Cell-Derived Exosomes. The Journal of Cell Biology, 147(3), 599–610. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151184/
Zitvogel, L., Regnault, A., Lozier, A., Wolfers, J., Flament, C., Tenza, D., Ricciardi-Castagnoli, P., Raposo, G., & Amigorena, S. (1998). Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes. Nature Medicine, 4(5), 594–600. https://doi.org/10.1038/nm0598-594
Ullah, I., Subbarao, R., & Rho, G. (2015). Human mesenchymal stem cells - current trends and future prospective. Bioscience Reports, 35(2), 1–18. https://doi.org/10.1042/bsr20150025
Chandra, A. (2023). Mesenchymal Stem Cell Biology. Mayo Clinic. https://www.mayo.edu/research/labs/bone-injury-repair/research/mesenchymal-stem-cell-biology#
Rao, D., Huang, D., Sang, C., Zhong, T., Zhang, Z., & Tang, Z. (2022). Advances in Mesenchymal Stem Cell-Derived Exosomes as Drug Delivery Vehicles. Frontiers in Bioengineering and Biotechnology, 9. https://doi.org/10.3389/fbioe.2021.797359
Lee, J.-K., Park, S.-R., Jung, B.-K., Jeon, Y.-K., Lee, Y.-S., Kim, M.-K., Kim, Y.-G., Jang, J.-Y., & Kim, C.-W. (2013). Exosomes Derived from Mesenchymal Stem Cells Suppress Angiogenesis by Down-Regulating VEGF Expression in Breast Cancer Cells. PLoS ONE, 8(12), e84256. https://doi.org/10.1371/journal.pone.0084256
Lou, G., Song, X., Yang, F., Wu, S., Wang, J., Chen, Z., & Liu, Y. (2015). Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. Journal of Hematology & Oncology, 8(1). https://doi.org/10.1186/s13045-015-0220-7
Sun, Y., Liu, G., Zhang, K., Cao, Q., Liu, T., & Li, J. (2021). Mesenchymal stem cells-derived exosomes for drug delivery. Stem Cell Research & Therapy, 12(1). https://doi.org/10.1186/s13287-021-02629-7
Yassine, S., & Alaaeddine, N. (2021). Mesenchymal Stem Cell Exosomes and Cancer: Controversies and Prospects. Advanced Biology, 6(2), 2101050. https://doi.org/10.1002/adbi.202101050
Dzierzak, E., & Philipsen, S. (2013). Erythropoiesis: Development and Differentiation. Cold Spring Harbor Perspectives in Medicine, 3(4), a011601–a011601. https://doi.org/10.1101/cshperspect.a011601
Kuo, W. P., Tigges, J. C., Toxavidis, V., & Ghiran, I. (2017). Red Blood Cells: A Source of Extracellular Vesicles. Methods in Molecular Biology (Clifton, N.J.), 1660, 15–22. https://doi.org/10.1007/978-1-4939-7253-1_2
Kalra, A., & Tuma, F. (2018, December 18). Physiology, Liver. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK535438/
Perets, N., Betzer, O., Shapira, R., Brenstein, S., Angel, A., Sadan, T., Ashery, U., Popovtzer, R., & Offen, D. (2019). Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders. Nano Letters, 19(6), 3422–3431. https://doi.org/10.1021/acs.nanolett.8b04148
Yang, L., Huang, S., Zhang, Z., Liu, Z., & Zhang, L. (2022). Roles and Applications of Red Blood Cell-Derived Extracellular Vesicles in Health and Diseases. International Journal of Molecular Sciences, 23(11), 5927. https://doi.org/10.3390/ijms23115927
Xu, Y., Luo, F., Liu, Y., Shi, L., Lu, X., Xu, W., & Liu, Q. (2015). Exosomal miR-21 derived from arsenite-transformed human bronchial epithelial cells promotes cell proliferation associated with arsenite carcinogenesis. Archives of Toxicology, 89(7), 1071–1082. https://doi.org/10.1007/s00204-014-1291-x
Qiao, L., Hu, S., Huang, K., Su, T., Li, Z., Vandergriff, A., Cores, J., Dinh, P.-U., Allen, T., Shen, D., Liang, H., Li, Y., & Cheng, K. (2020). Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs. Theranostics, 10(8), 3474–3487. https://doi.org/10.7150/thno.39434
Lu, Y., Huang, W., Li, M., & Zheng, A. (2023). Exosome-Based Carrier for RNA Delivery: Progress and Challenges. Pharmaceutics, 15(2), 598–598. https://doi.org/10.3390/pharmaceutics15020598
Lennaárd, A. J., Mamand, D. R., Wiklander, R. J., EL Andaloussi, S., & Wiklander, O. P. B. (2021). Optimised Electroporation for Loading of Extracellular Vesicles with Doxorubicin. Pharmaceutics, 14(1), 38. https://doi.org/10.3390/pharmaceutics14010038
Li, Y., Xing, L., Wang, L., Liu, X., Wu, L., Ni, M., Zhou, Z., Li, L., Liu, X., & Huang, Y. (2023). Milk-derived exosomes as a promising vehicle for oral delivery of hydrophilic biomacromolecule drugs. Asian Journal of Pharmaceutical Sciences, 18(2), 100797. https://doi.org/10.1016/j.ajps.2023.100797
Sedykh, S., Kuleshova, A., & Nevinsky, G. (2020). Milk Exosomes: Perspective Agents for Anticancer Drug Delivery. International Journal of Molecular Sciences, 21(18), 6646. https://doi.org/10.3390/ijms21186646
Xia, J., Miao, Y., Wang, X., Huang, X., & Dai, J. (2022). Recent progress of dendritic cell-derived exosomes (Dex) as an anti-cancer nanovaccine. Biomedicine & Pharmacotherapy, 152, 113250. https://doi.org/10.1016/j.biopha.2022.113250
Dendritic Cell-derived Exosomes (DEX)-based Vaccines - Creative Biolabs. (n.d.). Www.creative-Biolabs.com. Retrieved January 3, 2024, from https://www.creative-biolabs.com/exosome/dendritic-cell-derived-exosomes-dex-based-vaccines.htm
Elashiry, M., Elsayed, R., & Cutler, C. W. (2021). Exogenous and Endogenous Dendritic Cell-Derived Exosomes: Lessons Learned for Immunotherapy and Disease Pathogenesis. Cells, 11(1), 115. https://doi.org/10.3390/cells11010115
Elham Oveili, Somayeh Vafaei, Haniyeh Bazavar, Eslami, Y., Ehsan Mamaghanizadeh, Saman Yasamineh, & Omid Gholizadeh. (2023). The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases. 21(1). https://doi.org/10.1186/s12964-022-01017-9
Wei, W., Ao, Q., Wang, X., Cao, Y., Liu, Y., Zheng, S. G., & Tian, X. (2020). Mesenchymal Stem Cell-Derived Exosomes: A Promising Biological Tool in Nanomedicine. Frontiers in Pharmacology, 11, 590470. https://doi.org/10.3389/fphar.2020.590470
Ma, S.-R., Xia, H.-F., Gong, P., & Yu, Z.-L. (2023). Red Blood Cell-Derived Extracellular Vesicles: An Overview of Current Research Progress, Challenges, and Opportunities. Biomedicines, 11(10), 2798. https://doi.org/10.3390/biomedicines11102798
Sadeghi, S., Tehrani, F. R., Tahmasebi, S., Shafiee, A., & Hashemi, S. M. (2023). Exosome engineering in cell therapy and drug delivery. Inflammopharmacology. https://doi.org/10.1007/s10787-022-01115-7
Tian, J., Han, Z., Song, D., Peng, Y., Xiong, M., Chen, Z., Duan, S., & Zhang, L. (2023). Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications. International Journal of Nanomedicine, Volume 18, 7923–7940. https://doi.org/10.2147/ijn.s444582
Li, X., Corbett, A. L., Taatizadeh, E., Tasnim, N., Little, J. P., Garnis, C., Daugaard, M., Guns, E., Hoorfar, M., & Li, I. T. S. (2019). Challenges and opportunities in exosome research—Perspectives from biology, engineering, and cancer therapy. APL Bioengineering, 3(1), 011503. https://doi.org/10.1063/1.5087122
Roser, M., & Ritchie, H. (2019, November). Cancer. Our World in Data. https://ourworldindata.org/cancer
Panigrahi, A. R., Srinivas, L., & Panda, J. (2022). Exosomes: Insights and therapeutic applications in cancer. Translational Oncology, 21, 101439. https://doi.org/10.1016/j.tranon.2022.101439
Makler, A., & Asghar, W. (2020). Exosomal biomarkers for cancer diagnosis and patient monitoring. Expert Review of Molecular Diagnostics, 20(4), 387–400. https://doi.org/10.1080/14737159.2020.1731308
Hannafon, B. N., Trigoso, Y. D., Calloway, C. L., Zhao, Y. D., Lum, D. H., Welm, A. L., Zhao, Z. J., Blick, K. E., Dooley, W. C., & Ding, W. Q. (2016). Plasma exosome microRNAs are indicative of breast cancer. Breast Cancer Research, 18(1). https://doi.org/10.1186/s13058-016-0753-x
Per Hydbring, Luigi De Petris, Zhang, Y., Brandén, E., Hirsh Koyi, Novak, M., Kanter, L., Hååg, P., Hurley, J., Vasisht Tadigotla, Zhu, B., Skog, J., Viktorsson, K., Ekman, S., & Lewensohn, R. (2018). Exosomal RNA-profiling of pleural effusions identifies adenocarcinoma patients through elevated miR-200 and LCN2 expression. Lung Cancer, 124, 45–52. https://doi.org/10.1016/j.lungcan.2018.07.018
Xue, X.-F., Zhao, Y., Wang, X., Qin, L., & Hu, R. (2019). Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma. 120(1), 135–142. https://doi.org/10.1002/jcb.27165
Fang, X., Lan, H., Jin, K., & Qian, J. (2023). Pancreatic cancer and exosomes: role in progression, diagnosis, monitoring, and treatment. Frontiers in Oncology, 13, 1149551. https://doi.org/10.3389/fonc.2023.1149551
Zhao, X., Wu, D., Ma, X., Wang, J., Hou, W., & Zhang, W. (2020). Exosomes as drug carriers for cancer therapy and challenges regarding exosome uptake. Biomedicine & Pharmacotherapy, 128, 110237. https://doi.org/10.1016/j.biopha.2020.110237
Huda, M. N., Nafiujjaman, M., Deaguero, I. G., Okonkwo, J., Hill, M. L., Kim, T., & Nurunnabi, M. (2021). Potential Use of Exosomes as Diagnostic Biomarkers and in Targeted Drug Delivery: Progress in Clinical and Preclinical Applications. ACS Biomaterials Science & Engineering, 7(6), 2106–2149. https://doi.org/10.1021/acsbiomaterials.1c00217
Xie, J., Zheng, Z., Tuo, L., Deng, X., Tang, H., Peng, C., & Zou, Y. (2023). Recent advances in exosome-based immunotherapy applied to cancer. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1296857
Feng, W., Dean, D. C., Hornicek, F. J., Shi, H., & Duan, Z. (2019). Exosomes promote pre-metastatic niche formation in ovarian cancer. Molecular Cancer, 18(1). https://doi.org/10.1186/s12943-019-1049-4
Zhang, Y., Li, J., Gao, W., & Xie, N. (2022). Exosomes as Anticancer Drug Delivery Vehicles: Prospects and Challenges. Frontiers in Bioscience-Landmark, 27(10), 293. https://doi.org/10.31083/j.fbl2710293
Downloads
Posted
Categories
License
Copyright (c) 2024 Aditya Bhaskara
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.