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Synthetic exosome

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Exosomes are small vesicles secreted by cells that play a crucial role in intercellular communication. They contain a variety of biomolecules, including proteins, nucleic acids and lipids, which can be transferred between cells to modulate cellular processes.[1] Exosomes have been increasingly acknowledged as promising therapeutic tool and delivery platforms due to unique biological properties.[1]

  1. Biocompatibility: Exosomes are naturally occurring particles in body, which makes them highly biocompatible and less likely to activate immune response.[2]
  2. Targeting ability: Exosomes are assembled to express specific proteins or peptides, allowing them to target specific cells or tissues.[3]
  3. Natural cargo carries: Exosomes can naturally transport a variety of biomolecules, including proteins, RNA and DNA, which can be used for therapeutic purposes.[4]

However, due to exosomes being small in size (30-150 nm), present in various biological fluids (such as blood, urine, saliva), sensitivity to environmental factors (such temperature, pH), complexity of drug loading efficiency, there are challenges associated with isolation, purification, delivery and drug payload.[2][5][6]

While application of exosomes is still in its early stages, approaches are being explored to produce exosome-like nanovesicles (ELNs or artificial exosomes) to overcome these challenges.[7][8]

ELNs are a type of engineered exosomes designed to modify the structure and enhance the function of natural exosomes.[7] The content of ELNs can be highly-customized to match with various medical needs, allowing for more precise control over their properties compared to natural exosomes. Additionally, ELNs can be modified with selectively expressed functional groups on the surface to enhance its targeting and uptake by cells or tissues.[3][9] For example, ELNs can be engineered to enhance their stability in fluids, to target specific cell types, such ascytosol of brain cells.[10] Further, ELNs could consistently deliver cargo mRNA with therapeutic catalase mRNA to the brain, attenuating neurotoxicity and neuroinflammation.[10]

Above all, ELNs' properties can be tailored by researchers for specific applications with precise controlling. ELNs hold great potential as a novel approach to meet medical needs, including immunologic therapy,[5][11] anti-tumor,[10][12] anti-aging[13] and regeneration.[13]

References

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  1. ^ a b Kalluri, Raghu; LeBleu, Valerie S. (2020-02-07). "The biology, function, and biomedical applications of exosomes". Science. 367 (6478). doi:10.1126/science.aau6977. ISSN 0036-8075. PMC 7717626. PMID 32029601.
  2. ^ a b EL Andaloussi, Samir; Mäger, Imre; Breakefield, Xandra O.; Wood, Matthew J. A. (2013-04-15). "Extracellular vesicles: biology and emerging therapeutic opportunities". Nature Reviews Drug Discovery. 12 (5): 347–357. doi:10.1038/nrd3978. ISSN 1474-1776. PMID 23584393. S2CID 205478102.
  3. ^ a b Kooijmans, Sander A.A.; Schiffelers, Raymond M.; Zarovni, Natasa; Vago, Riccardo (September 2016). "Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: New nanotools for cancer treatment". Pharmacological Research. 111: 487–500. doi:10.1016/j.phrs.2016.07.006. ISSN 1043-6618. PMID 27394168.
  4. ^ Wu, Yun-Long; Yin, Hui; Zhao, Feng; Li, Jun (2012-10-26). "Multifunctional Hybrid Nanocarriers Consisting of Supramolecular Polymers and Quantum Dots for Simultaneous Dual Therapeutics Delivery and Cellular Imaging". Advanced Healthcare Materials. 2 (2): 297–301. doi:10.1002/adhm.201200183. ISSN 2192-2640. PMID 23184583. S2CID 285805.
  5. ^ a b Vader, Pieter; Mol, Emma A.; Pasterkamp, Gerard; Schiffelers, Raymond M. (November 2016). "Extracellular vesicles for drug delivery". Advanced Drug Delivery Reviews. 106 (Pt A): 148–156. doi:10.1016/j.addr.2016.02.006. ISSN 0169-409X. PMID 26928656.
  6. ^ Kamerkar, Sushrut; LeBleu, Valerie S.; Sugimoto, Hikaru; Yang, Sujuan; Ruivo, Carolina F.; Melo, Sonia A.; Lee, J. Jack; Kalluri, Raghu (June 2017). "Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer". Nature. 546 (7659): 498–503. Bibcode:2017Natur.546..498K. doi:10.1038/nature22341. ISSN 0028-0836. PMC 5538883. PMID 28607485.
  7. ^ a b "Review for "Brain‐targeted exosome‐mimetic cell membrane nanovesicles with therapeutic oligonucleotides elicit anti‐tumor effects in glioblastoma animal models"". 2022-06-15. doi:10.1002/btm2.10426/v1/review4. {{cite journal}}: Cite journal requires |journal= (help)
  8. ^ Wang, Qi-long; Zhuang, XiaoYing; Sriwastva, Mukesh K.; Mu, Jingyao; Teng, Yun; Deng, Zhongbin; Zhang, Lifeng; Sundaram, Kumaran; Kumar, Anil; Miller, Donald; Yan, Jun; Zhang, Huang-Ge (2018). "Blood exosomes regulate the tissue distribution of grapefruit-derived nanovector via CD36 and IGFR1 pathways". Theranostics. 8 (18): 4912–4924. doi:10.7150/thno.27608. ISSN 1838-7640. PMC 6217058. PMID 30429877. S2CID 53304117.
  9. ^ Han, Jingxia; Wu, Ting; Jin, Jing; Li, Zhiyang; Cheng, Wenjun; Dai, Xintong; Yang, Kai; Zhang, Heng; Zhang, Zhiyuan; Zhang, Haohao; Fan, Rong; Zheng, Shaoting; Liu, Haoyang; Li, Yinan; Zhao, Huan (2022-10-21). "Exosome-like nanovesicles derived from Phellinus linteus inhibit Mical2 expression through cross-kingdom regulation and inhibit ultraviolet-induced skin aging". Journal of Nanobiotechnology. 20 (1): 455. doi:10.1186/s12951-022-01657-6. ISSN 1477-3155. PMC 9587628. PMID 36271377.
  10. ^ a b c Kojima, Ryosuke; Bojar, Daniel; Rizzi, Giorgio; Hamri, Ghislaine Charpin-El; El-Baba, Marie Daoud; Saxena, Pratik; Ausländer, Simon; Tan, Kelly R.; Fussenegger, Martin (2018-04-03). "Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment". Nature Communications. 9 (1): 1305. Bibcode:2018NatCo...9.1305K. doi:10.1038/s41467-018-03733-8. ISSN 2041-1723. PMC 5880805. PMID 29610454.
  11. ^ Pascucci, Luisa; Coccè, Valentina; Bonomi, Arianna; Ami, Diletta; Ceccarelli, Piero; Ciusani, Emilio; Viganò, Lucia; Locatelli, Alberta; Sisto, Francesca; Doglia, Silvia Maria; Parati, Eugenio; Bernardo, Maria Ester; Muraca, Maurizio; Alessandri, Giulio; Bondiolotti, Gianpietro (October 2014). "Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery". Journal of Controlled Release. 192: 262–270. doi:10.1016/j.jconrel.2014.07.042. ISSN 0168-3659. PMID 25084218.
  12. ^ Zhao, Jun; Long, Xin; Zhou, Min (2021), "Clearable Nanoparticles for Cancer Photothermal Therapy", Bio-Nanomedicine for Cancer Therapy, Advances in Experimental Medicine and Biology, vol. 1295, Cham: Springer International Publishing, pp. 121–134, doi:10.1007/978-3-030-58174-9_6, ISBN 978-3-030-58173-2, PMID 33543458, S2CID 231818126, retrieved 2023-05-06
  13. ^ a b Zhu, Mengxi; Li, Shan; Feng, Shuying; Wang, Haojie; Hu, Lina; Gao, Shegan; Yu, Yingjie; Liang, Gaofeng (2021-08-06). "Tumor-microenvironment Responsive Targeted Exosome-like Nanovesicles From Dunaliella Salina for Enhancing Gene/immune Combination Therapy". doi:10.21203/rs.3.rs-733290/v1. S2CID 238837996. Retrieved 2023-05-06. {{cite journal}}: Cite journal requires |journal= (help)
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