Citation: Yutong Chen, Shuting Guo, Mingrui Fan, Songlin Yang, Qiuxia Lin, Jiafeng Zou, Junyuan Xu, Tongtong Zheng, Kangtai He, Feng Gao, Yanzuo Chen. Exosome-liposome hybrid system with antioxidant and anti-inflammatory activities targeting glial cells for the treatment of central nervous system diseases[J]. Chinese Chemical Letters, ;2026, 37(9): 112027. doi: 10.1016/j.cclet.2025.112027 shu

Exosome-liposome hybrid system with antioxidant and anti-inflammatory activities targeting glial cells for the treatment of central nervous system diseases

Yutong Chen ^{a, 1} ,
Shuting Guo ^{a, 1} ,
Mingrui Fan ^a ,
Songlin Yang ^a ,
Qiuxia Lin ^a ,
Jiafeng Zou ^a ,
Junyuan Xu ^a ,
Tongtong Zheng ^a ,
Kangtai He ^a ,
Feng Gao ^{a, b, c} ,
Yanzuo Chen ^{a, b, *,}

a.
Pharmaceutical Engineering and Process of Chemical Engineering Research Center of Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b.
Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
c.
Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China

chenyz@ecust.edu.cn

Received Date: 25 July 2025
Revised Date: 23 October 2025
Accepted Date: 27 October 2025
Available Online: 28 October 2025

Figures(7)

Central nervous system diseases (CNSDs), such as Parkinson's disease (PD) and depression, have attracted considerable attention due to their high morbidity and mortality rates. Neuronal damage in CNSDs is primarily driven by inflammation and oxidative stress induced by activated astrocytes and microglia. Thus, new therapeutic strategies are urgently needed that not only enable effective drug delivery across the blood-brain barrier (BBB), but also specifically target lesions while exerting antioxidant and anti-inflammatory effects on glial cells. To address this challenge, we developed an exosome-liposome hybrid system targeting glial cells co-loaded with fisetin (FIS) and pioglitazone (PIO) (RMP7-EL-FIS-PIO). This hybrid system crosses the BBB through the B2 bradykinin receptor-mediated opening and takes advantage of the homing properties of exosomes to accumulate at the site of brain lesions in murine models of PD and of depression. Through receptor-ligand binding and phagocytosis, the hybrid system targets glial cells to deliver drugs that inhibit their activation, thus protecting neurons. Our study demonstrates the great potential of the developed exosome-liposome hybrid system for the targeted treatment of CNSDs.
- Central nervous system disease,
- Glial cells,
- Exosome-liposome hybrid system,
- Fisetin,
- Pioglitazone
1. [1]
  X. Zhou, Q.R. Smith, X. Liu, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 13 (2021) e1695. doi: 10.1002/wnan.1695
2. [2]
  Q. Zhang, Q. Jiang, K. Sa, et al., Phytother. Res. 37 (2023) 4885–4907. doi: 10.1002/ptr.7955
3. [3]
  Z. Vahidinia, S. Barati, A. Azami Tameh, et al., Neuropeptides 107 (2024) 102451. doi: 10.1016/j.npep.2024.102451
4. [4]
  L. Jin, J. Zhang, L. Nie, et al., Chin. Chem. Lett. 36 (2025) 110774. doi: 10.1016/j.cclet.2024.110774
5. [5]
  T. Liu, X. Han, X. Sun, et al., Chin. Chem. Lett. 36 (2025) 111170. doi: 10.1016/j.cclet.2025.111170
6. [6]
  L.L. Ji, T.T. Huang, L.L. Mao, et al., Kaohsiung J. Med. Sci. 39 (2023) 1002–1010. doi: 10.1002/kjm2.12745
7. [7]
  H. Adachi, A. Morizane, S. Torikoshi, et al., Stem Cells Transl. Med. 11 (2022) 767–777. doi: 10.1093/stcltm/szac033
8. [8]
  X. Tang, P. Deng, Y. Jiang, et al., Biomedicines 11 (2023) 2878. doi: 10.3390/biomedicines11112878
9. [9]
  H.S. Díaz, A. Ríos-Gallardo, D. Ortolani, et al., Antioxidants 11 (2022) 1928. doi: 10.3390/antiox11101928
10. [10]
  K. Ge, Z. Li, A. Wang, et al., ACS Nano 17 (2023) 2222–2234. doi: 10.1021/acsnano.2c08499
11. [11]
  Y. Rong, C. Ji, Z. Wang, et al., J. Neuroinflammation 18 (2021) 196. doi: 10.1186/s12974-021-02268-y
12. [12]
  M.S. Islam, H.Y. Shin, Y.J. Yoo, et al., Antioxidants 11 (2022) 1697. doi: 10.3390/antiox11091697
13. [13]
  S.S.U. Hassan, S. Samanta, R. Dash, et al., Front. Pharmacol. 13 (2022) 1015835. doi: 10.3389/fphar.2022.1015835
14. [14]
  N. Afroze, S. Pramodh, J. Shafarin, et al., Int. J. Mol. Sci. 23 (2022) 1707. doi: 10.3390/ijms23031707
15. [15]
  Y. Long, X.Q. Li, J. Deng, et al., Ageing Res. Rev. 93 (2024) 102160. doi: 10.1016/j.arr.2023.102160
16. [16]
  A.H. Shehata, A.F. Anter, S.M.N. Abdel Hafez, et al., Int. Immunopharmacol. 139 (2024) 112757. doi: 10.1016/j.intimp.2024.112757
17. [17]
  J. Li, Q. Long, H. Ding, et al., Adv. Sci. 11 (2024) e2308677. doi: 10.1002/advs.202308677
18. [18]
  L. Gong, X. Zhang, K. Ge, et al., Biomaterials 267 (2021) 120483. doi: 10.1016/j.biomaterials.2020.120483
19. [19]
  G. Cheng, Y. Liu, R. Ma, et al., Nanomicro Lett. 14 (2022) 105.
20. [20]
  H.J. Liu, P. Xu, Adv. Drug Deliv. Rev. 191 (2022) 114619. doi: 10.1016/j.addr.2022.114619
21. [21]
  S. Triarico, P. Maurizi, S. Mastrangelo, et al., Cancers 11 (2019) 824. doi: 10.3390/cancers11060824
22. [22]
  D.F. Emerich, R.L. Dean, C. Osborn, et al., Clin. Pharmacokinet. 40 (2001) 105–123. doi: 10.2165/00003088-200140020-00003
23. [23]
  H. Wu, Y. Wang, Z. Ren, et al., Chin. Chem. Lett. 36 (2025) 109996. doi: 10.1016/j.cclet.2024.109996
24. [24]
  D. Ribatti, V. Benagiano, D. Guidolin, Brain Sci. 13 (2023) 398. doi: 10.3390/brainsci13030398
25. [25]
  Y. Wang, S. Yuan, L. Zhou, et al., Int. J. Nanomedicine 20 (2025) 5059–5080. doi: 10.2147/ijn.s516840
26. [26]
  T. Zhu, Z. Chen, G. Jiang, et al., ACS Nano 17 (2023) 16770–16786. doi: 10.1021/acsnano.3c03456
27. [27]
  C. Xie, J. Liao, N. Zhang, et al., Chin. Chem. Lett. 35 (2024) 109149. doi: 10.1016/j.cclet.2023.109149
28. [28]
  M. Piffoux, A.K A Silva, C. Wilhelm, et al., ACS Nano 12 (2018) 6830–6842. doi: 10.1021/acsnano.8b02053
29. [29]
  V.M.R. Mythili, R.L. Rajendran, R. Arun, et al., Bioengineering 12 (2025) 92. doi: 10.3390/bioengineering12010092
30. [30]
  Y. Xue, M. Gu, C. Chen, et al., Mol. Med. Rep. 27 (2023) 85. doi: 10.3892/mmr.2023.12972
31. [31]
  F. Branco, J. Cunha, M. Mendes, et al., ACS Nano 18 (2024) 16359–16394. doi: 10.1021/acsnano.4c01790
32. [32]
  X. Xue, X. Wang, M. Pang, et al., J. Nanobiotechn. 22 (2024) 196. doi: 10.1145/3711129.3711165
33. [33]
  M.A. Smith-Cohn, N.B. Burley, S.A. Grossman, Curr. Neuropharmacol. 20 (2022) 1383–1399. doi: 10.2174/1570159x20999220131163504
34. [34]
  W. Hao, Y. Cui, Y. Fan, et al., J. Nanobiotechnology 19 (2021) 378. doi: 10.1186/s12951-021-01110-0
35. [35]
  S. Jokar, I.A. Marques, S. Khazaei, et al., Bioengineering 9 (2022) 243. doi: 10.3390/bioengineering9060243
36. [36]
  E.J. Park, M. Shimaoka, Methods Mol. Biol. 2668 (2023) 145–158. doi: 10.1007/978-1-0716-3203-1_12
37. [37]
  S.S. Palakurthi, B. Shah, S. Kapre, et al., Nanoscale Adv. 6 (2024) 5803–5826. doi: 10.1039/d4na00501e
38. [38]
  B.K. Jung, K.Y. Ryu, Exp. Mol. Med. 55 (2023) 2138–2146. doi: 10.1038/s12276-023-01098-7
39. [39]
  Q. Li, T.T. Wu, O.U. Akakuru, et al., Adv. Funct. Mater. 33 (2023) 2214826. doi: 10.1002/adfm.202214826
40. [40]
  P. Wen, Z. Sun, F. Gou, et al., Ageing Res. Rev. 104 (2025) 102667. doi: 10.1016/j.arr.2025.102667
41. [41]
  M. Umar, S. Muzammil, M.A. Zahoor, et al., Evid. Based Complem. Alternat. Med. 2022 (2022) 1005255.
42. [42]
  H. Chew, V.A. Solomon, A.N. Fonteh, Front. Physiol. 11 (2020) 598. doi: 10.3389/fphys.2020.00598
43. [43]
  H. Yu, Q. Chang, T. Sun, et al., Ageing Res. Rev. 90 (2023) 102032. doi: 10.1016/j.arr.2023.102032
44. [44]
  W.H. Chang, H.T. Hsu, C.C. Lin, et al., Int. J. Mol. Sci. 25 (2024) 2514. doi: 10.3390/ijms25052514
45. [45]
  J. Li, Y. He, J. Fu, et al., Front. Nutr. 9 (2023) 1121789. doi: 10.3389/fnut.2023.1121789
46. [46]
  Q. Zheng, H. Liu, H. Zhang, et al., Adv. Sci. 10 (2023) e2300758. doi: 10.1002/advs.202300758
47. [47]
  F. Hemmati, N. Valian, A. Ahmadiani, et al., Iran. J. Pharm. Res. 23 (2024) e144200.
48. [48]
  F.S. Mohammed, S.B. Omay, K.N. Sheth, et al., Expert Opin. Drug Deliv. 20 (2023) 55–73. doi: 10.1080/17425247.2023.2152001
49. [49]
  F.Q. Zhang, J.L. Jiang, J.T. Zhang, et al., Neural Regen. Res. 15 (2020) 242–250. doi: 10.4103/1673-5374.265544
50. [50]
  D.H. Jung, M.E. Pak, H.J. Lee, et al., Life 10 (2020) 240. doi: 10.3390/life10100240
51. [51]
  S.S. Elshama, M. El-Kenawy Ael, H.E. Osman, Iran. J. Basic Med. Sci. 19 (2016) 712–719.
52. [52]
  E. Domi, F.F. Caputi, P. Romualdi, et al., J. Neurosci. 39 (2019) 9864–9875. doi: 10.1523/jneurosci.1922-19.2019
53. [53]
  Y. Yin, T. Ju, D. Zeng, et al., Pharmacol. Res. 207 (2024) 107322. doi: 10.1016/j.phrs.2024.107322
54. [54]
  M. Ishiyama, H. Gotoh, S. Oe, et al., Mol. Neurobiol. 62 (2025) 1373–1387. doi: 10.1007/s12035-024-04345-8
55. [55]
  C. Zhao, C. Gao, Z. Yang, et al., Chin. Chem. Lett. 36 (2025) 111089. doi: 10.1016/j.cclet.2025.111089
56. [56]
  S. Matsui, T. Sasaki, D. Kohno, et al., Nat. Commun. 9 (2018) 4604. doi: 10.1038/s41467-018-07033-z
1. [1]
  Yuanyuan Zeng , Fang Liu , Jun Wang , Bianfei Shao , Tao He , Zhongzheng Xiang , Yan Wang , Shunyao Zhu , Tian Yang , Siting Yu , Changyang Gong , Lei Liu . Fisetin micelles precisely exhibit a radiosensitization effect by inhibiting PDGFRβ/STAT1/STAT3/Bcl-2 signaling pathway in tumor. Chinese Chemical Letters, 2025, 36(2): 109734-. doi: 10.1016/j.cclet.2024.109734
2. [2]
  Peishuang Yu , Bohan Chen , Bingyu Xie , Mengjiao Zhou , Chengying Wang , Shenshen Yang , Wei Huang , Yubo Li . Recent advances in oral hydrogel drug delivery system for disease treatment. Chinese Chemical Letters, 2026, 37(7): 111695-. doi: 10.1016/j.cclet.2025.111695
3. [3]
  Na Wang , Wang Luo , Huaiyi Shen , Huakai Li , Zejiang Xu , Zhiyuan Yue , Chao Shi , Hengyun Ye , Leping Miao . Crystal engineering regulation achieving inverse temperature symmetry breaking ferroelasticity in a cationic displacement type hybrid perovskite system. Chinese Chemical Letters, 2024, 35(5): 108696-. doi: 10.1016/j.cclet.2023.108696
4. [4]
  Sili Qing , Yuxi Xu , Shuai Gao , Li-Ping Jiang , Xiaoge Wu , Wenlei Zhu . An efficient and sustainable hybrid electrochemical system for heterogeneous electro-Fenton degradation of phenolic pollutants. Chinese Chemical Letters, 2026, 37(7): 112193-. doi: 10.1016/j.cclet.2025.112193
5. [5]
  Yu-Long Peng , Zhi-Yong Qiu , Peng Liu , Zhe Dong , Jun-Yong Wu , Fang Yang , Zai-Fang Li , Shi-Yong Liu . Tuning fluorination patterns on the central benzene core of acceptors for high-efficiency ternary organic solar cells. Chinese Journal of Structural Chemistry, 2026, 45(5): 100886-100886. doi: 10.1016/j.cjsc.2026.100886
6. [6]
  Ya-Ting Gao , Yi-Lin Zhu , Xiao-Yuan Wang , Li-Ya Liang , Meng-Li Liu , Shuai Chang , Han-Bin Xu , Da-Wei Li , Bin-Bin Chen . Pure organic electrophosphorochromism system. Chinese Chemical Letters, 2025, 36(11): 110855-. doi: 10.1016/j.cclet.2025.110855
7. [7]
  Linjie Ju , Zhongxi Huang , Qian Shen , Chan Fu , Shuanghe Li , Wenjie Duan , Chenfeng Xu , Weizhen An , Zhiqiang Zhai , Jifu Wei , Changmin Yu , Guoren Zhou . Glutathione depletion based Pt(Ⅳ) hybrid mesoporous organosilica delivery system to conquer cisplatin chemoresistance: A “one stone three birds” strategy. Chinese Chemical Letters, 2024, 35(10): 109450-. doi: 10.1016/j.cclet.2023.109450
8. [8]
  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
9. [9]
  Kangrong Yan , Ziqiu Shen , Yanchun Huang , Benfang Niu , Hongzheng Chen , Chang-Zhi Li . Curing the vulnerable heterointerface via organic-inorganic hybrid hole transporting bilayers for efficient inverted perovskite solar cells. Chinese Chemical Letters, 2024, 35(6): 109516-. doi: 10.1016/j.cclet.2024.109516
10. [10]
  Hui Guo , Wen-Wen Li , Mei-Yin Wu , Jian-Bo Hu , Jun Wang , Yun Liu , Yang Zou , Chu-Luo Yang , Kai-Lu Zheng . Indolizine-benzophenone hybrid acceptors enable TADF materials for bioimaging and photodynamic therapy in living cells. Chinese Chemical Letters, 2026, 37(1): 111721-. doi: 10.1016/j.cclet.2025.111721
11. [11]
  Shicheng Dong , Jun Zhu . Could π-aromaticity cross an unsaturated system to a fully saturated one?. Chinese Chemical Letters, 2024, 35(6): 109214-. doi: 10.1016/j.cclet.2023.109214
12. [12]
  Yixin Zhang , Ting Wang , Jixiang Zhang , Pengyu Lu , Neng Shi , Liqiang Zhang , Weiran Zhu , Nongyue He . Formation mechanism for stable system of nanoparticle/protein corona and phospholipid membrane. Chinese Chemical Letters, 2024, 35(4): 108619-. doi: 10.1016/j.cclet.2023.108619
13. [13]
  Lingyun Shen , Shenxiang Yin , Qingshu Zheng , Zheming Sun , Wei Wang , Tao Tu . A rechargeable and portable hydrogen storage system grounded on soda water. Chinese Chemical Letters, 2025, 36(3): 110580-. doi: 10.1016/j.cclet.2024.110580
14. [14]
  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
15. [15]
  Xiaoyu Zhang , Xin Yu . Solar-powered heterogeneous water disinfection nano-system. Chinese Journal of Structural Chemistry, 2025, 44(3): 100439-100439. doi: 10.1016/j.cjsc.2024.100439
16. [16]
  Li Li , Xue Ke , Shan Wang , Zhuo Jiang , Yuzheng Guo , Chunguang Kuai . Antioxidative strategies of 2D MXenes in aqueous energy storage system. Chinese Chemical Letters, 2025, 36(5): 110423-. doi: 10.1016/j.cclet.2024.110423
17. [17]
  Meng-Xin Liu , Xiao-Long Su , Pu Chen , Yan-Yan Liu , Jian-Peng Li , Li Zou , Ben Zhong Tang , Hai-Tao Feng . Sequential FRET system based on macrocyclic AIEgens for versatile photocatalysis. Chinese Chemical Letters, 2026, 37(4): 111516-. doi: 10.1016/j.cclet.2025.111516
18. [18]
  Lei Wang , Jianing Zhang , Jin Xiong , Wenbo Dai , Miaochang Liu , Xiaobo Huang , Yuye Chai , Yunxiang Lei , Zhengxu Cai , Minyu Zhu . Enhancing the phosphorescence performance of organic doped system by carbonylation of guests. Chinese Chemical Letters, 2026, 37(5): 111706-. doi: 10.1016/j.cclet.2025.111706
19. [19]
  Qiannan Cao , Yu Liang , Weiyi Xia , Anna Guo , Mingxia Jiang , Lai Yang , Qiaoyan Dong , Wenming Zheng , Yingli Yao , Siting Zhang , Huilin Yuan , Pijun Su , Rongmei Zhou , Songyu Xu , Bo Chen , Jing Yao , Huapan Fang , Huayu Tian . Polycation-based miRNA delivery system for choroidal neovascularization treatment. Chinese Chemical Letters, 2026, 37(9): 112031-. doi: 10.1016/j.cclet.2025.112031
20. [20]
  Han-Min Wang , Yan-Chen Li , Lu-Lu Sun , Ming-Ye Tang , Jia Liu , Jiahao Cai , Lei Dong , Jia Li , Yi Zang , Hai-Hao Han , Xiao-Peng He . Protein-encapsulated long-wavelength fluorescent probe hybrid for imaging lipid droplets in living cells and mice with non-alcoholic fatty liver. Chinese Chemical Letters, 2024, 35(11): 109603-. doi: 10.1016/j.cclet.2024.109603

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(7)
HTML views(0)

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