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

  1. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 "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. 1 2 3 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. 1 2 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)