Citation: Meng Sun, Leijie Yu, Lu Bai, Xingyou Liu, Ying Xiong, Xia Zhao, Xing Zhong, Mengqiong Ran, Yu Wang, Xinlei Yan, Chenhui Wang, Robert J. Lee, Yaqin Tang, Wuyang He, Jing Xie. Cellular-nanoporation boosts high-yield RVG-modified exosomes for multifunctional α-synuclein scavengers against Parkinson's disease[J]. Chinese Chemical Letters, ;2026, 37(7): 111948. doi: 10.1016/j.cclet.2025.111948 shu

Cellular-nanoporation boosts high-yield RVG-modified exosomes for multifunctional α-synuclein scavengers against Parkinson's disease

Meng Sun ^{a, b, 1} ,
Leijie Yu ^{a, b, 1} ,
Lu Bai ^{a, b} ,
Xingyou Liu ^{a, b} ,
Ying Xiong ^c ,
Xia Zhao ^{a, b} ,
Xing Zhong ^{a, b} ,
Mengqiong Ran ^{a, b} ,
Yu Wang ^{a, b} ,
Xinlei Yan ^{a, b} ,
Chenhui Wang ^{d, e} ,
Robert J. Lee ^{a, b} ,
Yaqin Tang ^{a, b, *,} ,
Wuyang He ^{f, *,} ,
Jing Xie ^{a, b, *,}

a.
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
b.
Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, Chongqing 400054, China
c.
Enrollment and Employment Department, Alumni-Office, Chongqing University of Technology, Chongqing 400054, China
d.
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China
e.
School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
f.
The Second Affiniated Hospital of Chongqing Medical University, Chongqing 400010, China

tangyaqin@cqut.edu.cn

wuyanghe.311@outlook.com

xiejing33@cqut.edu.cn

Received Date: 12 May 2025
Revised Date: 9 October 2025
Accepted Date: 12 October 2025
Available Online: 16 October 2025

Figures(3)

The pathological protein α-synuclein (α-Syn) aggregates are considered a key toxic substance responsible for the degeneration of dopaminergic neurons in Parkinson's disease (PD). Clearing these pathological aggregates can potentially control PD progression at its source. However, conventional drug delivery systems face significant challenges, including the blood-brain barrier (BBB) and lack of tissue-specific targeting. To address this, we developed a core-shell hybrid system, named RExo-si-TN-T10, for the co-delivery of triptolide (T10) and small interfering RNA targeting α-Syn (siSNCA). This system comprises two components: an outer shell of exosomes (RExo) derived from BV2 microglial cells and modified with rabies virus glycoprotein peptide (RVG), and an inner core of a nanomicelle composed of phenylboronic acid derivatives: 4-Nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl carbonate (NBC) and trimethyl chitosan (TMC) for co-delivering gene and small-molecule drugs. Furthermore, we utilized cellular nanoporation (CNP) technology to significantly enhance exosome yield and transfection efficiency. This innovative nano-scavenger effectively eliminates α-Syn aggregates and reduces their cytotoxic effects in PD-affected neurons. Following treatment with RExo-si-TN-T10, we observed significant improvement in the motor behavior of PD mice. Our findings suggest that RExo-si-TN-T10 holds promise as a therapeutic platform for PD.
- Parkinson's disease,
- Targeted delivery,
- ROS response,
- Exosome,
- α-Syn,
- RNAi,
- BBB
1. [1]
  M.M. Hoehn, M.D. Yahr, Neurology 17 (1967) 427–442. doi: 10.1212/WNL.17.5.427
2. [2]
  B.W. Chang, Y.G. Jiang, C.X. Feng, et al., Food Sci. Hum. Wellness 14 (2025) 9250066. doi: 10.26599/fshw.2024.9250066
3. [3]
  Y. Zhuo, W.S. Li, W. Lu, et al., Mil. Med. Res. 11 (2024) 48.
4. [4]
  W. Poewe, K. Seppi, C.M. Tanner, et al., Nat. Rev. Dis. Primers 3 (2017) 17014. doi: 10.1038/nrdp.2017.14
5. [5]
  D.W. Dickson, H. Braak, J.E. Duda, et al., Lancet Neurol. 8 (2009) 1150–1157. doi: 10.1016/S1474-4422(09)70238-8
6. [6]
  X.H. Gao, H.R. Liu, J.J. Tang, L.B. Liu, Y.Z. Liu, Drug Dev. Res. 80 (2019) 438–445. doi: 10.1002/ddr.21515
7. [7]
  Y.Q. Wu, Z.S. Wang, Y. Ge, et al., J. Control. Release 370 (2024) 747–762. doi: 10.3390/cryst14080747
8. [8]
  J.P. Gao, S. Sun, W.W. Li, Y.P. Chen, D.F. Cai, Neurosci. Bull. 24 (2008) 133–142. doi: 10.1007/s12264-008-1225-9
9. [9]
  G.Z. Hu, X.L. Gong, L. Wang, et al., Mol. Neurobiol. 54 (2017) 2361–2372. doi: 10.1007/s12035-016-9808-3
10. [10]
  W.M. Pardridge, Adv. Drug Deliv. Rev. 59 (2007) 141–152. doi: 10.1016/j.addr.2007.03.008
11. [11]
  P. Anand, A.B. Kunnumakkara, R.A. Newman, B.B. Aggarwal, Mol. Pharm. 4 (2007) 807–818. doi: 10.1021/mp700113r
12. [12]
  N.J. Abbott, Cell. Mol. Neurobiol. 25 (2005) 5–23. doi: 10.1007/s10571-004-1374-y
13. [13]
  H. Kadry, B. Noorani, L. Cucullo, Fluids Barriers CNS 17 (2020) 69. doi: 10.1186/s12987-020-00230-3
14. [14]
  D.E. Tylawsky, H. Kiguchi, J. Vaynshteyn, et al., Nat. Mater. 22 (2023), 391–399. doi: 10.1038/s41563-023-01481-9
15. [15]
  H.L. Zhong, Y.F. Fang, M.C. Luo, et al., ACS Appl. Mater. Interfaces 16 (2024) 28209–28221. doi: 10.1021/acsami.4c04677
16. [16]
  Z.W. Fang, L.Y. Wang, X.Y. Zhang, et al., Int. J. Biol. Macromol. 284 (2025) 138233. doi: 10.1016/j.ijbiomac.2024.138233
17. [17]
  G. Song, C.L. Zeng, J.R. Li, et al., Nanomedicine 20 (2025) 1167–1180. doi: 10.1080/17435889.2025.2493037
18. [18]
  M. Xu, T. Feng, B.W. Liu, et al., Theranostics 11 (2021) 8926–8944. doi: 10.7150/thno.62330
19. [19]
  D. Rufino-Ramos, P.R. Albuquerque, V. Carmona, et al., J. Control. Release 262 (2017) 247–258. doi: 10.1016/j.jconrel.2017.07.001
20. [20]
  F. Ji, L.X. Xu, K.L. Long, et al., Transl. Res. 259 (2023) 1–12.
21. [21]
  Q.H. Wang, S. Cheng, F. Qin, et al., RSC Adv. 11 (2021), 8505–8515. doi: 10.1039/d1ra00550b
22. [22]
  L.Q. Chen, Z.M. Zhang, Y.H. Liu, et al., Chin. Chem. Lett. 36 (2025) 110228. doi: 10.1016/j.cclet.2024.110228
23. [23]
  P. Wang, Y. Wang, P. Li, et al., Chin. Chem. Lett. 34 (2023) 107691. doi: 10.1016/j.cclet.2022.07.034
24. [24]
  Z.W. Fang, X.Y. Zhang, H. Huang, J. Wu, Chin. Chem. Lett. 33 (2022) 1693–1704. doi: 10.1016/j.cclet.2021.11.050
25. [25]
  Z.G. Yang, J.F. Shi, J. Xie, et al., Nat. Biomed. Eng. 4 (2020) 69–83.
26. [26]
  M.H. Yan, X. Wang, X. Zhu, Free Radic. Biol. Med. 62 (2013) 90–101. doi: 10.1016/j.freeradbiomed.2012.11.014
27. [27]
  L.Y. Liu, Y. Li, H. Peng, et al., Sci. Adv. 6 (2020) eaba3967. doi: 10.1126/sciadv.aba3967
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2. [2]
  Zengchao Guo , Weiwei Liu , Tengfei Liu , Jinpeng Wang , Hui Jiang , Xiaohui Liu , Yossi Weizmann , Xuemei Wang . Engineered exosome hybrid copper nanoscale antibiotics facilitate simultaneous self-assembly imaging and elimination of intracellular multidrug-resistant superbugs. Chinese Chemical Letters, 2024, 35(7): 109060-. doi: 10.1016/j.cclet.2023.109060
3. [3]
  Xin-Yu Liu , He-Ying Mao , Jun-Sheng Hu , Tong-Rui Dou , Ben-Chi Liu , Chang-Xiu Lin , Jing-Shu Piao , Ming-Guan Piao . A c(RGDyK)-modified ROS-responsive polymeric micelle for hepatic stellate cell targeting. Chinese Chemical Letters, 2026, 37(1): 111237-. doi: 10.1016/j.cclet.2025.111237
4. [4]
  Cui-Ting Yang , Dan-Dan Wang , Shuai Chen , Jian-Mei Yang , Jun-Nan He , Jun-Hui Zhang , Xiao-Qing Liu , Jin Zhang , Lei Zhang , Yan Zhao . A chiral supramolecular nanocatcher prepared by d-biotin-pillar[5]arene for the selective capture and targeted delivery of oxaliplatin enantiomers. Chinese Chemical Letters, 2025, 36(9): 110820-. doi: 10.1016/j.cclet.2025.110820
5. [5]
  Juan Tao , Jinlong Yang , Mengyu Zhao , Quangang Zhu , Zhongjian Chen , Jianping Qi . Emerging trends in permeation-enhancing technologies for oral peptide delivery. Chinese Chemical Letters, 2026, 37(3): 111170-. doi: 10.1016/j.cclet.2025.111170
6. [6]
  Mengyue Li , Yue Zheng , Zhijun Lu , Yu Yang , Jiangping Lei , Yi Teng , Wanyi Zhou , Yiman Ge , Chunhui Wu , Hong Yang , Yiyao Liu . Aptamer-targeted and pH-responsive DNA tetrahedron for survivin mRNA fluorescence imaging and chemo/gene therapy. Chinese Chemical Letters, 2026, 37(6): 111541-. doi: 10.1016/j.cclet.2025.111541
7. [7]
  Yangyang Zhang , Lu Qiu , Houying Li , Wenli Cai , Ergang Liu , Hongtao Zhang , Bahtiyor Muhitdinov , Jianming Liang , Yongzhuo Huang . Biomimetically engineered plant-derived exosomes-like nanovesicles for rheumatoid arthritis therapy. Chinese Chemical Letters, 2025, 36(9): 110658-. doi: 10.1016/j.cclet.2024.110658
8. [8]
  Fengjie Liu , Fansu Meng , Zhenjiang Yang , Huan Wang , Yuehong Ren , Yu Cai , Xingwang Zhang . Exosome-biomimetic nanocarriers for oral drug delivery. Chinese Chemical Letters, 2024, 35(9): 109335-. doi: 10.1016/j.cclet.2023.109335
9. [9]
  Longhui Hao , Yi Zhang , Ying Sun , Yanqi Han , Jun Ye , Hongliang Wang , Lili Gao , Dong Wang , Yue Gao , Yanfang Yang , Yuling Liu . Advances in nano-delivery systems for targeted natural product delivery to specific skin layers in disease therapy and skin care. Chinese Chemical Letters, 2026, 37(7): 111597-. doi: 10.1016/j.cclet.2025.111597
10. [10]
  Xiaoxiao Wang , Bolun Wang , Fenfen Ji , Jie Yan , Jiacheng Fang , Doudou Zhang , Ji Xu , Jing Ji , Xinran Hao , Hemi Luan , Yanjun Hong , Shulan Qiu , Min Li , Zhu Yang , Wenlan Liu , Xiaodong Cai , Zongwei Cai . Discovery of plasma biomarkers for Parkinson’s disease diagnoses based on metabolomics and lipidomics. Chinese Chemical Letters, 2024, 35(11): 109653-. doi: 10.1016/j.cclet.2024.109653
11. [11]
  Tao Liu , Xuwei Han , Xueyi Sun , Weijie Zhang , Ke Gao , Runan Min , Yuting Tian , Caixia Yin . An activated fluorescent probe to monitor NO fluctuation in Parkinson’s disease. Chinese Chemical Letters, 2025, 36(3): 110170-. doi: 10.1016/j.cclet.2024.110170
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]
  Luqing Zhao , Dan Dou , Di Zhang , Shuqing Wang , Xihan Zhu , Ning Ding , Shengsheng Zhang , Chao Li . Nanotechnology-based natural remedies: Advancing inflammatory bowel disease treatment through targeted drug delivery. Chinese Chemical Letters, 2026, 37(5): 111262-. doi: 10.1016/j.cclet.2025.111262
14. [14]
  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
15. [15]
  Yingqiang Liang , Shilun Li , Yixiao Pan , Weiyu Zhang , Shupeng Liu , Yiwen Chen , Jiangfeng Hu , Xueliang Zhang , Jun Zhao , Zhigang Zheng . Exosome-hybridized hydrogel acts as a foamy protective coat for the liver. Chinese Chemical Letters, 2025, 36(11): 110841-. doi: 10.1016/j.cclet.2025.110841
16. [16]
  Jiajie Gu , Jiaxiang Gu , Lei Yu . Selenium and Alzheimer's disease. Chinese Chemical Letters, 2025, 36(8): 110727-. doi: 10.1016/j.cclet.2024.110727
17. [17]
  Jia-Lun Duan , Xin-Lan Zhang , Li-Qiang Zhao , Ya-Nan Liu , An-Ni Yao , Nian-Guang Li , Jin-Ao Duan , Chun-Jie Bao . Macrophage membrane-camouflaged nanoparticles for targeted drug delivery. Chinese Chemical Letters, 2026, 37(7): 111610-. doi: 10.1016/j.cclet.2025.111610
18. [18]
  Yujie Li , Ya-Nan Wang , Yin-Gen Luo , Hongcai Yang , Jinrui Ren , Xiao Li . Advances in synthetic biology-based drug delivery systems for disease treatment. Chinese Chemical Letters, 2024, 35(11): 109576-. doi: 10.1016/j.cclet.2024.109576
19. [19]
  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
20. [20]
  Mengmeng Yuan , Xiwen Hu , Na Li , Limin Xu , Mengxi Zhu , Xing Pei , Rui Li , Lu Sun , Yupeng Chen , Fei Yu , Huining He . Kidney targeted delivery of siRNA mediated by peptide-siRNA conjugate for the treatment of acute kidney injury. Chinese Chemical Letters, 2025, 36(6): 110251-. doi: 10.1016/j.cclet.2024.110251

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