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
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