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
1. [1]
  Ju Wang , Yongbing Sun , Lingbang Meng , Jianfang Feng , Meng Cheng , Liangxing Tu . Intestinal transporters and oral absorption enhancing strategies based on these transporters. Chinese Chemical Letters, 2025, 36(5): 110529-. doi: 10.1016/j.cclet.2024.110529
2. [2]
  Yang Xu , Le Ma , Yang Wang , Chunmeng Shi . Engineering strategies of biomaterial-assisted exosomes for skin wound repair: Latest advances and challenges. Chinese Chemical Letters, 2025, 36(1): 109766-. doi: 10.1016/j.cclet.2024.109766
3. [3]
  Junjie Wang , Yan Wang , Zhengdong Li , Changqiang Xie , Musammir Khan , Xingzhou Peng , Fabiao Yu . Triphenylamine-AIEgens photoactive materials for cancer theranostics. Chinese Chemical Letters, 2024, 35(6): 108934-. doi: 10.1016/j.cclet.2023.108934
4. [4]
  Jingwen Zhao , Jianpu Tang , Zhen Cui , Limin Liu , Dayong Yang , Chi Yao . A DNA micro-complex containing polyaptamer for exosome separation and wound healing. Chinese Chemical Letters, 2024, 35(9): 109303-. doi: 10.1016/j.cclet.2023.109303
5. [5]
  Yunyan Li , Zimin Cai , Zhicheng Wang , Sifeng Zhu , Wendian Liu , Cheng Wang . Construction of biomimetic hybrid nanovesicles based on M1 macrophage-derived exosomes for therapy of cancer. Chinese Chemical Letters, 2025, 36(4): 109942-. doi: 10.1016/j.cclet.2024.109942
6. [6]
  Linghui Zou , Meng Cheng , Kaili Hu , Jianfang Feng , Liangxing Tu . Vesicular drug delivery systems for oral absorption enhancement. Chinese Chemical Letters, 2024, 35(7): 109129-. doi: 10.1016/j.cclet.2023.109129
7. [7]
  Qiang Li , Jiangbo Fan , Hongkai Mu , Lin Chen , Yongzhen Yang , Shiping Yu . Nucleus-targeting orange-emissive carbon dots delivery adriamycin for enhanced anti-liver cancer therapy. Chinese Chemical Letters, 2024, 35(6): 108947-. doi: 10.1016/j.cclet.2023.108947
8. [8]
  Liqing Chen , Zheming Zhang , Yanhong Liu , Chenfei Liu , Congcong Xiao , Liming Gong , Mingji Jin , Zhonggao Gao , Wei Huang . Systemically intravenous siRNA delivery into brain with a targeting and efficient polypeptide carrier and its evaluation on anti-glioma efficacy. Chinese Chemical Letters, 2025, 36(3): 110228-. doi: 10.1016/j.cclet.2024.110228
9. [9]
  Qin Yu , Haisheng He , Jianping Qi , Yi Lu , Wei Wu . Oral delivery of insulin by barbed microneedles actuated by intestinal peristalsis. Chinese Chemical Letters, 2024, 35(9): 109888-. doi: 10.1016/j.cclet.2024.109888
10. [10]
  Jiaqi Huang , Renjiang Kong , Yanmei Li , Ni Yan , Yeyang Wu , Ziwen Qiu , Zhenming Lu , Xiaona Rao , Shiying Li , Hong Cheng . Feedback enhanced tumor targeting delivery of albumin-based nanomedicine to amplify photodynamic therapy by regulating AMPK signaling and inhibiting GSTs. Chinese Chemical Letters, 2024, 35(8): 109254-. doi: 10.1016/j.cclet.2023.109254
11. [11]
  Wen Xiao , Fazhan Wang , Yangzhuo Gu , Xi He , Na Fan , Qian Zheng , Shugang Qin , Zhongshan He , Yuquan Wei , Xiangrong Song . PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines. Chinese Chemical Letters, 2024, 35(5): 108755-. doi: 10.1016/j.cclet.2023.108755
12. [12]
  Junfei Yang , Ke Wang , Shuxin Sun , Tianqi Pei , Junxiu Li , Xunwei Gong , Cuixia Zheng , Yun Zhang , Qingling Song , Lei Wang . A "spore-like" oral nanodrug delivery platform for precision targeted therapy of inflammatory bowel disease. Chinese Chemical Letters, 2025, 36(3): 110180-. doi: 10.1016/j.cclet.2024.110180
13. [13]
  Zhaojing Huang , Hao Li , Jiayi Luo , Shunxing Li , Ming Zhao , Fengjiao Liu , Haijiao Xie . Deep learning-based simultaneous bioavailability assessment and speciation analysis of dissolved organic copper. Chinese Chemical Letters, 2025, 36(5): 110209-. doi: 10.1016/j.cclet.2024.110209
14. [14]
  Jiechen Liu , Xiaoguang Li , Ruiyang Xia , Yuqi Wang , Fenghe Zhang , Yongzhi Pang , Qing Li . Efficient suppression of oral squamous cell carcinoma through spatial dimension conversion drug delivery systems-enabled immunomodulatory-photodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109619-. doi: 10.1016/j.cclet.2024.109619
15. [15]
  Lingjun Sha , Bing Bo , Jiayu Li , Qi Liu , Ya Cao , Jing Zhao . Precise assessment of lung cancer-derived exosomes based on dual-labelled membrane interface. Chinese Chemical Letters, 2025, 36(4): 110109-. doi: 10.1016/j.cclet.2024.110109
16. [16]
  Han Han , Bi-Te Chen , Jia-Rong Ding , Jin-Ming Si , Tian-Jiao Zhou , Yi Wang , Lei Xing , Hu-Lin Jiang . A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy. Chinese Chemical Letters, 2024, 35(10): 109583-. doi: 10.1016/j.cclet.2024.109583
17. [17]
  Shaoqing Du , Xinyong Liu , Xueping Hu , Peng Zhan . Targeting novel sites represents an effective strategy for combating drug resistance. Chinese Chemical Letters, 2025, 36(1): 110378-. doi: 10.1016/j.cclet.2024.110378
18. [18]
  Lu-Lu He , Lan-Tu Xiong , Xin Wang , Yu-Zhen Li , Jia-Bao Li , Yu Shi , Xin Deng , Zi-Ning Cui . Application of inhibitors targeting the type III secretion system in phytopathogenic bacteria. Chinese Chemical Letters, 2025, 36(4): 110044-. doi: 10.1016/j.cclet.2024.110044
19. [19]
  Xi Chen , Xue Zhang , Shuai Yang , Jie Wang , Tian Tang , Maling Gou . An adhesive hydrogel for the treatment of oral ulcers. Chinese Chemical Letters, 2025, 36(3): 110021-. doi: 10.1016/j.cclet.2024.110021
20. [20]
  Weijian Zhang , Xianyu Deng , Liying Wang , Jian Wang , Xiuting Guo , Lianggui Huang , Xinyi Wang , Jun Wu , Linjia Jiang . Poly(ferulic acid) nanocarrier enhances chemotherapy sensitivity of acute myeloid leukemia by selectively targeting inflammatory macrophages. Chinese Chemical Letters, 2024, 35(9): 109422-. doi: 10.1016/j.cclet.2023.109422

Get Citation

PDF

XML

Metrics

PDF Downloads(4)
Abstract views(519)
HTML views(18)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142