Citation: Weiqun Li, Ming-Jie Dong, Haibing Dai, Shanming Lu, Ran Luo, Jiahui Cao, Fan Zhang, Lin Mei, Jianbo Yu. Application of mitochondrial miRNA-204 nanoprobes in Alzheimer's disease treatment by clearing reactive oxygen species-mediated autophagy[J]. Chinese Chemical Letters, ;2025, 36(8): 110614. doi: 10.1016/j.cclet.2024.110614 shu

Application of mitochondrial miRNA-204 nanoprobes in Alzheimer's disease treatment by clearing reactive oxygen species-mediated autophagy

Weiqun Li ^{a, 1} ,
Ming-Jie Dong ^{c, 1} ,
Haibing Dai ^a ,
Shanming Lu ^a ,
Ran Luo ^b ,
Jiahui Cao ^b ,
Fan Zhang ^{a, *,} ,
Lin Mei ^{b, *,} ,
Jianbo Yu ^{a, *,}

a.
Longgang Central Hospital, Shenzhen 518116, China
b.
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
c.
Guangdong Laboratory of Artificial Intelligent and Digital Economy (SZ), Shenzhen 518107, China

zhangfan@bme.pumc.edu.cn

meilin@bme.pumc.edu.cn

jianboyu2001@vip.sina.com

Received Date: 6 July 2024
Revised Date: 30 October 2024
Accepted Date: 3 November 2024
Available Online: 5 November 2024

Figures(4)

Neuronal mitochondrial damage is the primary characteristic of Alzheimer's disease (AD); as mitochondrial microRNAs (miRNAs) are crucial for maintaining mitochondrial function, developing a detection system for mitochondrial miRNAs and applying it for AD treatment is of great significance. Herein, we report CeO₂-DNA-RNA hybrid chain (DRP)/mitochondrial aptamers (MA) nanoclusters, formed using specially modified 5 nm sized cerium dioxide (CeO₂) nanoparticles, to achieve AD diagnosis and treatment by targeting mitochondrial miRNA-204. First, nanomaterials with unique reactive oxygen species-scavenging functions could easily enter the central nervous system, and surface modification with mitochondrial aptamers facilitated successful mitochondrial targeting. Furthermore, surface modification of nanomaterials with DNA-RNA hybrid biological detection probes was used to detect miRNA-204 in AD and simultaneously perform gene-silencing therapy. In 3×Tg-AD model mice, CeO₂-DRP/MA aggregated into neuronal mitochondria, silenced mitochondrial miRNA-204, and restored the damaged mitochondria for AD treatment. The promising diagnostic and therapeutic functions of CeO₂-DRP/MA demonstrate its better performance as a diagnostic and therapeutic system targeting mitochondrial miRNA.
- Mitochondrial miRNA-204,
- Alzheimer's disease,
- Diagnosis and treatment,
- miRNA regulation
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