Preview

Успехи молекулярной онкологии

Расширенный поиск

Экзосомы молока в качестве агентов доставки терапевтически значимых препаратов при онкологических заболеваниях

https://doi.org/10.17650/2313-805X-2022-9-2-23-31

Аннотация

Экзосомы – это природные нановезикулы диаметром 40–100 нм, принимающие активное участие в переносе различных биологически активных веществ, а также в межклеточной коммуникации. Природное происхождение обусловливает биологическую совместимость экзосом с культурами клеток и делает их перспективными средствами доставки противоопухолевых препаратов. В настоящее время методы искусственного получения данных нановезикул не разработаны. Препараты экзосом, полученные из опухолевых клеток, непригодны для терапии. Молоко –биологическая жидкость, которая доступна в промышленных масштабах. Оно может быть универсальным источником экзосом, используемых в лечении онкологических заболеваний. Адресная доставка противоопухолевых препаратов при помощи экзосом молока позволяет снизить токсический эффект цитостатических средств, используемых в химиотерапии. В данном обзоре рассмотрены методы выделения экзосом из молока, их дополнительная очистка, анализ биологически значимых компонентов этих везикул – белков и нуклеиновых кислот, а также перспективы применения экзосом молока в терапии онкологических заболеваний.

Об авторах

С. Е. Седых
ФГБУН «Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук»; ФГБОУ ВО «Новосибирский национальный исследовательский государственный университет»
Россия

Сергей Евгеньевич Седых

630090 Новосибирск, проспект Академика Лаврентьева, 8;

630090 Новосибирск, ул. Пирогова, 2



А. М. Тимофеева
ФГБУН «Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук»
Россия

630090 Новосибирск, проспект Академика Лаврентьева, 8



А. Е. Кулешова
ФГБУН «Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук»
Россия

630090 Новосибирск, проспект Академика Лаврентьева, 8



Г. А. Невинский
ФГБУН «Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук»; ФГБОУ ВО «Новосибирский национальный исследовательский государственный университет»
Россия

630090 Новосибирск, проспект Академика Лаврентьева, 8;

630090 Новосибирск, ул. Пирогова, 2



Список литературы

1. Colombo M., Raposo G., Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014;30:255–89. DOI: 10.1146/annurev-cellbio-101512-122326.

2. Sawada S.I., Sato Y.T., Kawasaki R. et al. Nanogel hybrid assembly for exosome intracellular delivery: Effects on endocytosis and fusion by exosome surface polymer engineering. Biomater Sci 2020;8:619–30. DOI: 10.1039/c9bm01232j.

3. Bunggulawa E.J., Wang W., Yin T. et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnology 2018;16:81. DOI: 10.1186/s12951-018-0403-9.

4. Admyre C., Johansson S.M., Qazi K.R. et al. Exosomes with immune modulatory features are present in human breast milk. J Immunol 2007;179(3):1969–78. DOI: 10.4049/jimmunol.179.3.1969.

5. Yamada T., Inoshima Y., Matsuda T., Ishiguro N. Comparison of methods for isolating exosomes from bovine milk. J Vet Med Sci 2012;74(11):1523–5. DOI: 10.1292/jvms.12-0032.

6. Gu Y., Li M., Wang T., et al. Lactationrelated microRNA expression profiles of porcine breast milk exosomes. PLoS One 2012;7. DOI: 10.1371/journal.pone.0043691.

7. Modepalli V., Kumar A., Hinds L.A. et al. Differential temporal expression of milk miRNA during the lactation cycle of the marsupial tammar wallaby (Macropus eugenii). BMC Genomics 2014;15:1012. DOI: 10.1186/1471-2164-15-1012.

8. Yassin A.M., Abdel Hamid M.I., Farid O.A. et al. Dromedary milk exosomes as mammary transcriptome nano-vehicle: their isolation, vesicular and phospholipidomic characterizations. J Adv Res 2016;7:749–56. DOI: 10.1016/j.jare.2015.10.003. Available at: https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-15-1012.

9. Hock A., Miyake H., Li B. et al. Breast milk-derived exosomes promote intestinal epithelial cell growth. J Pediatr Surg 2017;52(5):755–9. DOI:10.1016/j.jpedsurg.2017.01.032.

10. Sedykh S.E., Purvinish L.V., Monogarov A.S. et al. Purified horse milk exosomes contain an unpredictable small number of major proteins. Biochim Open 2017;4:61–72. DOI: 10.1016/j.biopen.2017.02.004.

11. Ma J., Wang C., Long K. et al. Exosomal microRNAs in giant panda (Ailuropoda melanoleuca) breast milk: Potential maternal regulators for the development of newborn cubs. Sci Rep 2017;7:1–11. DOI: 10.1038/s41598-017-03707-8.

12. Gao H.N., Guo H.Y., Zhang H. et al. Yak milk-derived exosomes promote proliferation of intestinal epithelial cells in hypoxic environment. J Dairy Sci 2019;102(2):985–96. DOI: 10.3168/jds.2018-14946.

13. González M.I., Martín-Duque P., Desco M., Salinas B. Radioactive labeling of milk-derived exosomes with 99mTc and in vivo tracking by SPECT imaging. Nanomaterials 2020;10(6):1062. DOI: 10.3390/nano10061062.

14. Sedykh S.E., Kuleshova A.E., Purvinsh L.V. et al. Horse milk exosomes: isolation, microscopic and biochemical analysis, and prospects of use. Biotekhnologiya 2020;36(5):62–71. DOI: 10.21519/0234-2758-2020-36-5-62-71.

15. Agrawal A.K., Aqil F., Jeyabalan J. et al. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine 2017;13(5):1627–36. DOI: 10.1016/j.nano.2017.03.001.

16. Munagala R., Aqil F., Jeyabalan J., Gupta R.C. Bovine milk-derived exosomes for drug delivery. Cancer Lett 2016;371(1):48–61. DOI: 10.1016/j.canlet.2015.10.020.

17. Aqil F., Munagala R., Jeyabalan J. et al. Milk exosomes – natural nanoparticles for siRNA delivery. Cancer Lett 2019;449:186–95. DOI: 10.1016/j.canlet.2019.02.011.

18. Théry C., Witwer K.W., Aikawa E. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018;7(1):1535750. DOI: 10.1080/20013078.2018.1535750.

19. Zonneveld M.I., Brisson A.R., van Herwijnen M.J.C. et al. Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures. J Extracell Vesicles 2014;3:24215. DOI: 10.3402/jev.v3.24215.

20. Blans K., Hansen M.S., Sørensen L.V. et al. Pellet-free isolation of human and bovine milk extracellular vesicles by size-exclusion chromatography. J Extracell Vesicles 2017;6(1): 1294340. DOI: 10.1080/20013078.2017.1294340.

21. De la Torre Gomez C., Goreham R.V., Bech Serra J.J. et al. “Exosomics” – a review of biophysics, biology and biochemistry of exosomes with a focus on human breast milk. Front Genet 2018;9. DOI: 10.3389/fgene.2018.00092.

22. Sedykh S.E., Purvinish L.V., Burkova E.E. et al. Analysis of peptides and small proteins in preparations of horse milk exosomes, purified on anti-CD81- Sepharose. Int Dairy J 2021;117:104994. DOI: 10.1016/j.idairyj.2021.104994.

23. Chen T., Xi Q.-Y., Sun J.-J. et al. Revelation of mRNAs and proteins in porcine milk exosomes by transcriptomic and proteomic analysis. BMC Vet Res 2017;13(1). DOI: 10.1186/s12917-017-1021-8.

24. Liao Y., Alvarado R., Phinney B., Lönnerdal B. Proteomic characterization of human milk whey proteins during a twelve-month lactation period. J Proteome Res 2011;10(4):1746–54. DOI: 10.1021/pr101028k.

25. Reinhardt T.A., Lippolis J.D., Nonnecke B.J., Sacco RE. Bovine milk exosome proteome. J Proteomics 2012;75(5):1486–92. DOI: 10.1016/j.jprot.2011.11.017.

26. Van Herwijnen M.J.C., Zonneveld M.I., Goerdayal S. et al. Comprehensive proteomic analysis of human milk-derived extracellular vesicles unveils a novel functional proteome distinct from other milk components. Mol Cell Proteomics 2016;15(11):3412–23. DOI: 10.1074/mcp.M116.060426.

27. Sverdlov E.D. Amedeo Avogadro’s cry: what is 1 μg of exosomes? Bioessays 2012;34(10):873–5. DOI: 10.1002/bies.201200045.

28. Sedykh S.E., Burkova E.E., Purvinsh L.V. et al. Milk exosomes: isolation, biochemistry, morphology, and perspectives of use. In: Extracellular vesicles and their importance in human health. Rijeka, Croatia: IntechOpen; 2020.

29. Burkova E.E., Dmitrenok P.S., Bulgakov D.V. et al. Exosomes from human placenta purified by affinity chromatography on sepharose bearing immobilized antibodies against CD81 tetraspanin contain many peptides and small proteins. IUBMB Life 2018;70(11):1144–55. DOI: 10.1002/iub.1928.

30. Koh Y.Q., Peiris H.N., Vaswani K. et al. Characterization of exosomes from body fluids of dairy cows. J Anim Sci 2017;95(9):3893–904. DOI: 10.2527/jas2017.1727.

31. Yang M., Song D., Cao X. et al. Comparative proteomic analysis of milkderived exosomes in human and bovine colostrum and mature milk samples by iTRAQ-coupled LC-MS/MS. Food Res Int 2017;92:17–25. DOI: 10.1016/j.foodres.2016.11.041.

32. Samuel M., Chisanga D., Liem M. et al. Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth. Sci Rep 2017;7(1):5933. DOI: 10.1038/s41598-017-06288-8.

33. Benmoussa A., Gotti C., Bourassa S. et al. Identification of protein markers for extracellular vesicle (EV) subsets in cow’s milk. J Proteomics 2019;192. DOI: 10.1016/j.jprot.2018.08.010.

34. Reinhardt T.A., Sacco R.E., Nonnecke B.J., Lippolis J.D. Bovine milk proteome: quantitative changes in normal milk exosomes, milk fat globule membranes and whey proteomes resulting from Staphylococcus aureus mastitis. J Proteomics 2013;82:141–54. DOI: 10.1016/j.jprot.2013.02.013.

35. Burgoyne R.D., Duncan J.S. Secretion of milk proteins. J Mammary Gland Biol Neoplasia 1998;3(3):275–86. DOI: 10.1023/a:1018763427108.

36. Hata T., Murakami K., Nakatani H. et al. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs. Biochem Biophys Res Commun 2010;396(2):528–33. DOI: 10.1016/j.bbrc.2010.04.135.

37. Kosaka N., Izumi H., Sekine K., Ochiya T. MicroRNA as a new immuneregulatory agent in breast milk. Silence 2010;1(1):7. DOI: 10.1186/1758-907X-1-7.

38. Izumi H., Kosaka N., Shimizu T. et al. Time-dependent expression profiles of microRNAs and mRNAs in rat milk whey. PLoS One 2014;9(2):e88843. DOI: 10.1371/journal.pone.0088843.

39. Izumi H., Tsuda M., Sato Y. et al. Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages. J Dairy Sci 2015;98(5):2920–33. DOI: 10.3168/jds.2014-9076.

40. Zhang L., Chen T., Yin Y. et al. Dietary microRNA – a novel functional component of food. Adv Nutr 2019;10(4):711–21. DOI: 10.1093/advances/nmy127.

41. Benmoussa A., Provost P. Milk microRNAs in health and disease. Compr rev food sci food saf 2019;18(3):703–22. DOI: 10.1111/1541-4337.12424.

42. Skotland T., Hessvik N.P., Sandvig K., Llorente A. Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology. J Lipid Res 2019;60(1):9–18. DOI: 10.1194/jlr.R084343.

43. Smyth T., Kullberg M., Malik N. et al. Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J Control Release 2015;199:145–55. DOI: 10.1016/j.jconrel.2014.12.013.

44. Chen Z., Xie Y., Luo J. et al. Milk exosome-derived miRNAs from water buffalo are implicated in immune response and metabolism process. BMC Vet Res 2020;16(1):123. DOI:10.1186/s12917-020-02339-x.

45. Leiferman A., Shu J., Upadhyaya B. et al. Storage of extracellular vesicles in human milk, and microrna profiles in human milk exosomes and infant formulas. J Pediatr Gastroenterol Nutr 2019;69(2):235–8. DOI: 10.1097/MPG.0000000000002363.

46. Chen T., Xi Q.-Y., Ye R.-S. et al. Exploration of microRNAs in porcine milk exosomes. BMC Genomics 2014;15(1):100. DOI: 10.1186/1471-2164-15-100.

47. Kim K.-U., Kim W.-H., Jeong C.H. et al. More than Nutrition: therapeutic potential of breast milk-derived exosomes in cancer. Int J Mol Sci 2020;21(19):7327. DOI: 10.3390/ijms21197327.

48. Mirza A.H., Kaur S., Nielsen L.B. et al. Breast milk-derived extracellular vesicles enriched in exosomes from mothers with type 1 diabetes contain aberrant levels of microRNAs. Front Immunol 2019;10:2543. DOI: 10.3389/fimmu.2019.02543.

49. Quan S., Nan X., Wang K. et al. Characterization of sheep milk extracellular vesicle-miRNA by sequencing and comparison with cow milk. Animals 2020;10(2):331. DOI: 10.3390/ani10020331.

50. Hagiwara K., Ochiya T., Kosaka N. A paradigm shift for extracellular vesicles as small RNA carriers: from cellular waste elimination to therapeutic applications. Drug Deliv Transl Res 2014;4(1):31–7. DOI: 10.1007/s13346-013-0180-9.

51. Somiya M., Yoshioka Y., Ochiya T. Biocompatibility of highly purified bovine milk-derived extracellular vesicles. J Extracell Vesicles 2018;7(1):1440132. DOI: 10.1080/20013078.2018.1440132.

52. Badawy A.A., El-Magd M.A., AlSadrah S.A. Therapeutic effect of camel milk and itsexosomes on MCF7 cells in vitro and in vivo. Integr Cancer Ther 2018;17(4):1235–46. DOI: 10.1177/1534735418786000.

53. Carobolante G., Mantaj J., Ferrari E., Vllasaliu D. Cow milk and intestinal epithelial cell-derived extracellular vesicles as systems for enhancing oral drug delivery. Pharmaceutics 2020;12(3):226. DOI: 10.3390/pharmaceutics12030226.

54. Betker J.L., Angle B.M., Graner M.W., Anchordoquy T.J. The potential of exosomes from cow milk for oral delivery. J Pharm Sci 2019;108(4):1496–1505. DOI: 10.1016/j.xphs.2018.11.022.

55. Li D., Yao S., Zhou Z. et al. Hyaluronan decoration of milk exosomes directs tumor-specific delivery of doxorubicin. Carbohydr Res 2020;493:108032. DOI: 10.1016/j.carres.2020.108032.

56. Munagala R., Aqil F., Jeyabalan J. et al. Exosomal formulation of anthocyanidins against multiple cancer types. Cancer Lett 2017;393:94–102. DOI: 10.1016/j.canlet.2017.02.004.

57. Aqil F., Kausar H., Agrawal A.K. et al. Exosomal formulation enhances therapeutic response of celastrol against lung cancer. Exp Mol Pathol 2016;101(1):12–21. DOI: 10.1016/j.yexmp.2016.05.013.

58. Tatiparti K., Sau S., Kashaw S., Iyer A. siRNA Delivery strategies: a comprehensive review of recent developments. Nanomaterials 2017;7(4):77. DOI: 10.3390/nano7040077.

59. Shandilya S., Rani P., Onteru S.K., Singh D. Small interfering RNA in milk exosomes is resistant to digestion and crosses the intestinal barrier in vitro. J Agric Food Chem 2017;65(43):9506–13. DOI: 10.1021/acs.jafc.7b03123.


Рецензия

Для цитирования:


Седых С.Е., Тимофеева А.М., Кулешова А.Е., Невинский Г.А. Экзосомы молока в качестве агентов доставки терапевтически значимых препаратов при онкологических заболеваниях. Успехи молекулярной онкологии. 2022;9(2):23-31. https://doi.org/10.17650/2313-805X-2022-9-2-23-31

For citation:


Sedykh S.E., Timofeeva A.M., Kuleshova A.E., Nevinskiy G.A. Milk exosomes as delivery agents for therapy of cancer diseases. Advances in Molecular Oncology. 2022;9(2):23-31. (In Russ.) https://doi.org/10.17650/2313-805X-2022-9-2-23-31

Просмотров: 276


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2313-805X (Print)
ISSN 2413-3787 (Online)