Citation: Fengjie Liu, Fansu Meng, Zhenjiang Yang, Huan Wang, Yuehong Ren, Yu Cai, Xingwang Zhang. Exosome-biomimetic nanocarriers for oral drug delivery[J]. Chinese Chemical Letters, ;2024, 35(9): 109335. doi: 10.1016/j.cclet.2023.109335 shu

Exosome-biomimetic nanocarriers for oral drug delivery

Fengjie Liu ^{a, 1} ,
Fansu Meng ^{b, 1} ,
Zhenjiang Yang ^{c, 1} ,
Huan Wang ^a ,
Yuehong Ren ^a ,
Yu Cai ^{a, *,} ,
Xingwang Zhang ^{a, d, *,}

a.
Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou 511443, China
b.
Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of TCM, Zhongshan 528400, China
c.
Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China
d.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 511443, China

yezq@szu.edu.cn

chengm@szu.edu.cn

Received Date: 4 November 2023
Revised Date: 20 November 2023
Accepted Date: 21 November 2023
Available Online: 23 November 2023

Figures(5)

Exosomes as authigenous nanovesicles secreted by living cells represent a significant class of biomaterials. By virtue of their unique roles in intercellular communication, exosomes can mediate intercellular information/cargoes exchange as messenger and facilitate drug delivery as smart vehicles. Oral medication is the most clinically relied upon route of administration and can achieve both topical and systemic therapeutic effects after absorption. Exosomes and exosome-derived vectors have shown to be of high value in oral drug delivery, since they enable efficient oral delivery of therapeutic molecules by targeting intestinal epithelial cells. In recent years, exosome-biomimetic nanocarriers have emerged as an important catalyzer in innovating oral drug delivery systems. In this work, we roundly reviewed the biogenesis and functions of exosomes, their extraction and characterization methods, resources available for exosomes harvest, and design philosophy of exosome-derived vehicles, particularly highlighting the oral delivery application of exosome-biomimetic nanocarriers for diverse medicines. Accumulating evidence suggests that exosome-biomimetic nanocarriers hold great promise for oral delivery of intractable drugs with potential biopharmaceutic issues.
- Exosomes,
- Oral delivery,
- Biomimetic nanocarriers,
- Targeting,
- Bioavailability
1. [1]
  R. Kalluri, V.S. LeBleu, Science 367 (2020) eaau6977. doi: 10.1126/science.aau6977
2. [2]
  T. Wang, Y. Fu, S. Sun, et al., Chin. Chem. Lett. 34 (2023) 107508. doi: 10.1016/j.cclet.2022.05.022
3. [3]
  Y. Zhang, Y. Liu, H. Liu, et al., Cell Biosci. 9 (2019) 19. doi: 10.1186/s13578-019-0282-2
4. [4]
  C. Marar, B. Starich, D. Wirtz, Nat. Immunol. 22 (2021) 560–570. doi: 10.1038/s41590-021-00899-0
5. [5]
  A. Butreddy, N. Kommineni, N. Dudhipala, Nanomaterials 11 (2021) 1481. doi: 10.3390/nano11061481
6. [6]
  M.I. Mosquera-Heredia, L.C. Morales, O.M. Vidal, et al., Biomedicines 9 (2021) 1061. doi: 10.3390/biomedicines9081061
7. [7]
  W. Nie, J. Chen, B. Wang, et al., MedComm Biomater. Appl. 1 (2022) e10.
8. [8]
  D. Donoso-Meneses, A.I. Figueroa-Valdés, M. Khoury, et al., Pharmaceutics 15 (2023) 716. doi: 10.3390/pharmaceutics15030716
9. [9]
  J.L. Betker, B.M. Angle, M.W. Graner, et al., J. Pharm. Sci. 108 (2019) 1496–1505. doi: 10.1016/j.xphs.2018.11.022
10. [10]
  Y. Ren, L. Nie, S. Zhu, et al., Int. J. Nanomed. 17 (2022) 4861–4877. doi: 10.2147/IJN.S382192
11. [11]
  J. Rezaie, M. Feghhi, T. Etemadi, Cell Commun. Signal. 20 (2022) 145. doi: 10.1186/s12964-022-00959-4
12. [12]
  S. Gurung, D. Perocheau, L. Touramanidou, et al., Cell Commun. Signal. 19 (2021) 47. doi: 10.1186/s12964-021-00730-1
13. [13]
  L.M. Doyle, M.Z. Wang, Cells 8 (2019) 727. doi: 10.3390/cells8070727
14. [14]
  S. Xie, Q. Zhang, L. Jiang, Membranes 12 (2022) 498. doi: 10.3390/membranes12050498
15. [15]
  D.W. Greening, S.K. Gopal, R. Xu, et al., Semin. Cell Dev. Biol. 40 (2015) 72–81. doi: 10.1016/j.semcdb.2015.02.009
16. [16]
  C. Li, Y.Q. Ni, H. Xu, et al., Signal Transduct. Target. Ther. 6 (2021) 383. doi: 10.1038/s41392-021-00779-x
17. [17]
  C. Bang, T. Thum, Int. J. Biochem. Cell Biol. 44 (2012) 2060–2064. doi: 10.1016/j.biocel.2012.08.007
18. [18]
  B. Zhou, K. Xu, X. Zheng, et al., Signal Transduct. Target. Ther. 5 (2020) 144. doi: 10.1038/s41392-020-00258-9
19. [19]
  Y. Lu, Z. Tong, Z. Wu, et al., Chin. Chem. Lett. 33 (2022) 3188–3192. doi: 10.1016/j.cclet.2021.12.045
20. [20]
  W. Lim, H.S. Kim, Tissue Eng. Regen. Med. 16 (2019) 213–223. doi: 10.1007/s13770-019-00190-2
21. [21]
  D. Ha, N. Yang, V. Nadithe, Acta Pharm. Sin. B 6 (2016) 287–296. doi: 10.1016/j.apsb.2016.02.001
22. [22]
  W.Z. Liu, Z.J. Ma, X.W. Kang, Anal. Bioanal. Chem. 414 (2022) 7123–7141. doi: 10.1007/s00216-022-04253-7
23. [23]
  Y. Jia, L. Yu, T. Ma, et al., Theranostics 12 (2022) 6548–6575. doi: 10.7150/thno.74305
24. [24]
  C. Coughlan, K.D. Bruce, O. Burgy, et al., Curr. Protoc. Cell Biol. 88 (2020) e110. doi: 10.1002/cpcb.110
25. [25]
  J. Gao, A. Li, J. Hu, et al., Front. Bioeng. Biotechnol. 10 (2022) 1100892.
26. [26]
  N. Resnik, R. Romih, M.E. Kreft, et al., J. Vis. Exp. 187 (2022) e63550.
27. [27]
  K. McNicholas, M.Z. Michael, Methods Mol. Biol. 1545 (2017) 35–42.
28. [28]
  T.K. Kurian, S. Banik, D. Gopal, et al., Mol. Biotechnol. 63 (2021) 249–266. doi: 10.1007/s12033-021-00300-3
29. [29]
  O. Janouskova, R. Herma, A. Semeradtova, et al., Front. Mol. Biosci. 9 (2022) 846650. doi: 10.3389/fmolb.2022.846650
30. [30]
  J. He, W. Ren, W. Wang, et al., Drug Deliv. Transl. Res. 12 (2022) 2385–2402. doi: 10.1007/s13346-021-01087-1
31. [31]
  L. Qiao, S. Hu, K. Huang, et al., Theranostics 10 (2020) 3474–3487. doi: 10.7150/thno.39434
32. [32]
  M.K. McDonald, Y. Tian, R.A. Qureshi, et al., Pain 155 (2014) 1527–1539. doi: 10.1016/j.pain.2014.04.029
33. [33]
  M.D. Hade, C.N. Suire, Z. Suo, Cells 10 (2021) 1959. doi: 10.3390/cells10081959
34. [34]
  Y. Liang, L. Duan, J. Lu, et al., Theranostics 11 (2021) 3183–3195. doi: 10.7150/thno.52570
35. [35]
  A. Ngu, S. Wang, H. Wang, et al., Am. J. Physiol. Cell Physiol. 322 (2022) C865–C874. doi: 10.1152/ajpcell.00029.2022
36. [36]
  T.T. Le, T. Van de Wiele, T.N. Do, et al., J. Dairy Sci. 95 (2012) 2307–2318. doi: 10.3168/jds.2011-4947
37. [37]
  H. Izumi, N. Kosaka, T. Shimizu, et al., J. Dairy Sci. 95 (2012) 4831–4841. doi: 10.3168/jds.2012-5489
38. [38]
  Y. Liao, X. Du, J. Li, et al., Mol. Nutr. Food Res. 61 (2017) 170082.
39. [39]
  M.R. Warren, C. Zhang, A. Vedadghavami, et al., Biomater. Sci. 9 (2021) 4260–4277. doi: 10.1039/D0BM01497D
40. [40]
  M.Y. Tian, D.X. Hao, Y. Liu, et al., Food Funct 14 (2023) 1320–1337. doi: 10.1039/D2FO02013K
41. [41]
  C. Yan, J. Chen, C. Wang, et al., Drug Deliv 29 (2022) 214–228. doi: 10.1080/10717544.2021.2023699
42. [42]
  H. Miyake, C. Lee, S. Chusilp, et al., Pediatr. Surg. Int. 36 (2020) 155–163. doi: 10.1007/s00383-019-04599-7
43. [43]
  A.F. Saleh, E. Lázaro-Ibáñez, M.A. Forsgard, et al., Nanoscale 11 (2019) 6990–7001. doi: 10.1039/C8NR08720B
44. [44]
  H.A. Dad, T.W. Gu, A.Q. Zhu, et al., Mol. Ther. 29 (2021) 13–31. doi: 10.1016/j.ymthe.2020.11.030
45. [45]
  J. Zhong, B. Xia, S. Shan, et al., Biomaterials 277 (2021) 121126. doi: 10.1016/j.biomaterials.2021.121126
46. [46]
  S.P. Li, Z.X. Lin, X.Y. Jiang, et al., Acta Pharmacol. Sin. 39 (2018) 542–551. doi: 10.1038/aps.2017.178
47. [47]
  C. Xu, Y. Kang, X. Dong, et al., Chin. Chem. Lett. 34 (2023) 107528. doi: 10.1016/j.cclet.2022.05.042
48. [48]
  L. Zheng, B. Hu, D. Zhao, et al., Chin. Chem. Lett. (2023) 108647.
49. [49]
  G. Liang, Y. Zhu, D.J. Ali, et al., J. Nanobiotechnol. 18 (2020) 10. doi: 10.1186/s12951-019-0563-2
50. [50]
  L. Zhao, C. Gu, Y. Gan, et al., J. Control. Release 318 (2020) 1–15. doi: 10.1016/j.jconrel.2019.12.005
51. [51]
  Y.T. Sato, K. Umezaki, S. Sawada, et al., Sci. Rep. 6 (2016) 21933. doi: 10.1038/srep21933
52. [52]
  Q. Zhan, K. Yi, X. Li, et al., Macromol. Biosci. 21 (2021) e2100042. doi: 10.1002/mabi.202100042
53. [53]
  X.M. Xi, S.J. Xia, R. Lu, Pharmazie 76 (2021) 61–67.
54. [54]
  P. Kumar, A. Nagarajan, P.D. Uchil, Cold Spring Harb. Protoc. 2019 (2019) 519–525.
55. [55]
  L. Alvarez-Erviti, Y. Seow, H. Yin, et al., Nat. Biotechnol. 29 (2011) 341–345. doi: 10.1038/nbt.1807
56. [56]
  T. Yong, X. Zhang, N. Bie, et al., Nat. Commun. 10 (2019) 3838. doi: 10.1038/s41467-019-11718-4
57. [57]
  M.J.W. Evers, S.I. van de Wakker, E.M. de Groot, et al., Adv. Healthca. Mater. 11 (2022) e2101202. doi: 10.1002/adhm.202101202
58. [58]
  L. Zou, M. Cheng, K. Hu, et al., Chin. Chem. Lett. 35 (2024) 109129. doi: 10.1016/j.cclet.2023.109129
59. [59]
  I. Zoya, H. He, L. Wang, et al., Chin. Chem. Lett. 32 (2021) 1545–1549. doi: 10.1016/j.cclet.2020.09.038
60. [60]
  K. Thapa Magar, G.F. Boafo, X. Li, et al., Chin. Chem. Lett. 33 (2022) 587–596. doi: 10.1016/j.cclet.2021.08.020
61. [61]
  P. Grossen, M. Portmann, E. Koller, et al., Eur. J. Pharm. Biopharm. 158 (2021) 198–210. doi: 10.1016/j.ejpb.2020.11.012
62. [62]
  T. Umezu, M. Takanashi, Y. Murakami, et al., Mol. Ther. Methods Clin. Dev. 21 (2021) 199–208. doi: 10.1016/j.omtm.2021.03.006
63. [63]
  Y. Mao, M. Han, C. Chen, et al., Nanoscale 13 (2021) 20157–20169. doi: 10.1039/D1NR06015E
64. [64]
  L. Wu, L. Wang, X. Liu, et al., Acta Pharm. Sin. B 12 (2022) 2029–2042. doi: 10.1016/j.apsb.2021.12.015
65. [65]
  Y. Shi, S. Guo, Y. Liang, et al., Curr. Pharm. Biotechnol. 23 (2022) 1072–1079. doi: 10.2174/1389201022666210820114236
66. [66]
  Y. Li, L. Xing, L. Wang, et al., Asian J. Pharm. Sci. 18 (2023) 100797. doi: 10.1016/j.ajps.2023.100797
67. [67]
  A.K. Agrawal, F. Aqil, J. Jeyabalan, et al., Nanomedicine 13 (2017) 1627–1636. doi: 10.1016/j.nano.2017.03.001
68. [68]
  R. Kandimalla, F. Aqil, S.S. Alhakeem, et al., Cancers 13 (2021) 3700. doi: 10.3390/cancers13153700
69. [69]
  K.T. Magar, G.F. Boafo, M. Zoulikha, et al., Chin. Chem. Lett. 34 (2023) 107453. doi: 10.1016/j.cclet.2022.04.051
70. [70]
  M. Vashisht, P. Rani, S.K. Onteru, et al., Appl. Biochem. Biotechnol. 183 (2017) 993–1007. doi: 10.1007/s12010-017-2478-4
71. [71]
  D. Sun, X. Zhuang, X. Xiang, et al., Mol. Ther. 18 (2010) 1606–1614. doi: 10.1038/mt.2010.105
72. [72]
  R. Munagala, F. Aqil, J. Jeyabalan, et al., Cancer Lett. 393 (2017) 94–102. doi: 10.1016/j.canlet.2017.02.004
73. [73]
  S. Qu, Y. Han, Y. Liu, et al., J. Agric. Food Chem. 70 (2022) 16069–16079. doi: 10.1021/acs.jafc.2c04971
74. [74]
  G. Carobolante, J. Mantaj, E. Ferrari, et al., Pharmaceutics 12 (2020) 226. doi: 10.3390/pharmaceutics12030226
75. [75]
  B. Li, C. Teng, H. Yu, et al., Acta Pharm. Sin. B 13 (2023) 2369–2382. doi: 10.1016/j.apsb.2022.12.002
76. [76]
  Q. Xiao, X. Li, C. Liu, et al., Acta Pharm. Sin. B 13 (2023) 3503–3517. doi: 10.1016/j.apsb.2022.07.012
77. [77]
  R. Munagala, F. Aqil, J. Jeyabalan, et al., Cancer Lett. 371 (2016) 48–61. doi: 10.1016/j.canlet.2015.10.020
78. [78]
  F. Aqil, J. Jeyabalan, A.K. Agrawal, et al., Food Funct. 8 (2017) 4100–4107. doi: 10.1039/C7FO00882A
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