Citation: Kai Wang, Yun Wang, Lihang Wang, Zhuhai Li, Xi Yu, Xuanhe You, Diwei Wu, Yueming Song, Jiancheng Zeng, Zongke Zhou, Shishu Huang, Yunfeng Lin. Therapeutic siRNA targeting CC chemokine receptor 2 loaded with tetrahedral framework nucleic acid alleviates neuropathic pain by regulating microglial polarization[J]. Chinese Chemical Letters, ;2025, 36(3): 109868. doi: 10.1016/j.cclet.2024.109868 shu

Therapeutic siRNA targeting CC chemokine receptor 2 loaded with tetrahedral framework nucleic acid alleviates neuropathic pain by regulating microglial polarization

Kai Wang ^{a, 1} ,
Yun Wang ^{b, 1} ,
Lihang Wang ^a ,
Zhuhai Li ^a ,
Xi Yu ^a ,
Xuanhe You ^a ,
Diwei Wu ^a ,
Yueming Song ^a ,
Jiancheng Zeng ^a ,
Zongke Zhou ^a ,
Shishu Huang ^{a, *,} ,
Yunfeng Lin ^{b, c, d, *,}

a.
Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
b.
State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
c.
Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu 610041, China
d.
National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China

h0794062@scu.edu.cn

yunfenglin@scu.edu.cn

Received Date: 17 February 2024
Revised Date: 1 April 2024
Accepted Date: 7 April 2024
Available Online: 8 April 2024

Figures(4)

Neuropathic pain (NP) is one of the most common pathological pain types and is associated with limited treatment options; moreover, it affects patients’ quality of life and causes a heavy social burden. Despite the emphasis on inhibiting neuronal apoptosis to relieve NP, the crucial role of a neuroinflammation is often overlooked. Therefore, refocusing on the regulation of microglia polarization to create a more conducive environment for neuron holds great potential in NP treatment. In recent years, small interfering RNAs (siRNAs) had become an attractive therapeutic option. However, an efficient loading and delivery system for siRNA is still in lack. In our study, a nanostructured tetrahedral framework nucleic acid loaded with the small interfering RNA C–C chemokine receptor 2 (T-siCCR2) was successfully designed and synthesized for use in NP rat model in vivo and in a lipopolysaccharide (LPS)-induced inflammatory environment in vitro. This nanoscale complex is endowed with structural stability and satisfactory delivery efficiency while assuring the silencing effect of siRNA-CCR2. In vivo, T-siCCR2 treatment exhibited favorable effects on pain relief and functional improvement in the NP animal model by directly targeting microglia. In vitro, T-siCCR2 counteracts LPS-induced inflammation by inhibiting the differentiation of microglia toward the M1 phenotype, thus playing a neuroprotective role. RNA sequencing was subsequently performed to elucidate the underlying mechanism involved. These results indicate that T-siCCR2 may serve as a potential treatment option for NP in the future.
- Neuropathic pain,
- Tetrahedral framework nucleic,
- Small interfering RNA,
- Microglial polarization,
- Neuronal apoptosis
1. [1]
  L. Colloca, T. Ludman, D. Bouhassira, et al., Nat. Rev. Dis. Primers 3 (2017) 17002. doi: 10.1038/nrdp.2017.2
2. [2]
  Q.G. Wang, J. Cheng, F. Liu, et al., Adv. Sci. 11 (2024) 2306622. doi: 10.1002/advs.202306622
3. [3]
  N.B. Finnerup, S. Haroutounian, P. Kamerman, et al., Pain 157 (2016) 1599–1606. doi: 10.1097/j.pain.0000000000000492
4. [4]
  A. Ellis, D.L.H. Bennett, Br. J. Anaesth. 111 (2013) 26–37. doi: 10.1093/bja/aet128
5. [5]
  S. Ghazisaeidi, M.M. Muley, M.W. Salter, Annu. Rev. Pharmacol. 63 (2023) 565–583. doi: 10.1146/annurev-pharmtox-051421-112259
6. [6]
  O. Tabatabaei-Malazy, P. Khashayar, P. Khashayar, B. Larijani, Aging Clin. Exp. Res. 34 (2022) S387–S388.
7. [7]
  M.Z. Xu, Y.H. Ji, Open Life Sci. 18 (2023) 20220567. doi: 10.1515/biol-2022-0567
8. [8]
  Y. Li, Z.W. Cai, W.J. Ma, et al., Bone Res. 12 (2024) 14. doi: 10.1038/s41413-024-00319-7
9. [9]
  C. Abbadie, J.A. Lindia, A.M. Cumiskey, et al., Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 7947–7952. doi: 10.1073/pnas.1331358100
10. [10]
  N.C. Seeman, H.F. Sleiman, Nat. Rev. Mater. 3 (2018) 17068. doi: 10.1038/natrevmats.2017.68
11. [11]
  Y. Chen, X.Y. Chen, B.W. Zhang, et al., Signal Transduct. Target. Ther. 9 (2024) 28. doi: 10.1038/s41392-024-01736-0
12. [12]
  C. Wiraja, Y. Zhu, D.C.S. Lio, et al., Nat. Commun. 10 (2019) 1147. doi: 10.1038/s41467-019-09029-9
13. [13]
  J.J. Li, Y.X. Yao, Y. Wang, et al., Adv. Mater. 34 (2022) 2202513. doi: 10.1002/adma.202202513
14. [14]
  D. Rosenblum, N. Joshi, W. Tao, et al., Nat. Commun. 9 (2018) 1410. doi: 10.1038/s41467-018-03705-y
15. [15]
  L. Bai, M.G. Feng, Q. Zhang, et al., Adv. Funct. Mater. (2024) 2314789.
16. [16]
  W. Ho, X.Q. Zhang, X.Y. Xu, Adv. Healthc. Mater. 5 (2016) 2715–2731. doi: 10.1002/adhm.201600418
17. [17]
  Q. Hu, L. Fang, F. Li, et al., Eur. J. Pain 19 (2015) 920–928. doi: 10.1002/ejp.618
18. [18]
  S.A. Liddelow, K.A. Guttenplan, L.E.C. Larke, et al., Nature 541 (2017) 481–487. doi: 10.1038/nature21029
19. [19]
  T. Berta, O. Poirot, M. Pertin, et al., Mol. Cell. Neurosci. 37 (2008) 196–208. doi: 10.1016/j.mcn.2007.09.007
20. [20]
  Y.H. Liu, S.H. Li, S.Y. Lin, et al., Chin. Chem. Lett. 34 (2023) 107987. doi: 10.1016/j.cclet.2022.107987
21. [21]
  D.Q. Zeng, Z.K. Ma, X. Zan, et al., Chin. Chem. Lett. 35 (2024) 108433. doi: 10.1016/j.cclet.2023.108433
22. [22]
  J.W. Zhang, J.H. Yan, Y.A. Wang, et al., Chin. Chem. Lett. 35 (2024) 108434. doi: 10.1016/j.cclet.2023.108434
23. [23]
  H.K. Erichsen, G. Blackburn-Munro, Pain 98 (2002) 151–161. doi: 10.1016/S0304-3959(02)00039-8
24. [24]
  I. Decosterd, C.J. Woolf, Pain 87 (2000) 149–158. doi: 10.1016/S0304-3959(00)00276-1
25. [25]
  J. Scholz, C.J. Woolf, Nat. Neurosci. 10 (2007) 1361–1368. doi: 10.1038/nn1992
26. [26]
  H.C. Huang, L. Chen, H.X. Zhang, et al., J. Mol. Neurosci. 58 (2016) 416–423. doi: 10.1007/s12031-015-0672-9
27. [27]
  D.X. Xiao, T.Y. Chen, T.X. Zhang, et al., Chin. Chem. Lett. 35 (2024) 108602. doi: 10.1016/j.cclet.2023.108602
28. [28]
  E.R. Wang, R. Han, M.Y. Wu, et al., Chin. Chem. Lett. 35 (2024) 108361. doi: 10.1016/j.cclet.2023.108361
29. [29]
  M. Hüttemann, P. Pecina, M. Rainbolt, et al., Mitochondrion 11 (2011) 369–381. doi: 10.1016/j.mito.2011.01.010
30. [30]
  E. Radi, P. Formichi, C. Battisti, A. Federico, J. Alzheimers Dis. 42 (2014) S125–S152. doi: 10.3233/jad-132738
31. [31]
  R.H. Shih, C.Y. Wang, C.M. Yang, Front. Mol. Neurosci. 8 (2015) 77. doi: 10.3389/fnmol.2015.00077
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2. [2]
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3. [3]
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6. [6]
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7. [7]
  Botao Gao , He Qi , Hui Liu , Jun Chen . Role of polarization evolution in the hysteresis effect of Pb-based antiferroelecrtics. Chinese Chemical Letters, 2024, 35(4): 108598-. doi: 10.1016/j.cclet.2023.108598
8. [8]
  Jing Guo , Zhi-Guo Lu , Rui-Chen Zhao , Bao-Ku Li , Xin Zhang . Nucleic acid therapy for metabolic-related diseases. Chinese Chemical Letters, 2025, 36(3): 109875-. doi: 10.1016/j.cclet.2024.109875
9. [9]
  Junhua Wang , Xin Lian , Xichuan Cao , Qiao Zhao , Baiyan Li , Xian-He Bu . Dual polarization strategy to enhance CH₄ uptake in covalent organic frameworks for coal-bed methane purification. Chinese Chemical Letters, 2024, 35(8): 109180-. doi: 10.1016/j.cclet.2023.109180
10. [10]
  Zhenyu Hu , Zhenchun Yang , Shiqi Zeng , Kun Wang , Lina Li , Chun Hu , Yubao Zhao . Cationic surface polarization centers on ionic carbon nitride for efficient solar-driven H₂O₂ production and pollutant abatement. Chinese Chemical Letters, 2024, 35(10): 109526-. doi: 10.1016/j.cclet.2024.109526
11. [11]
  Wen-Bo Wei , Qi-Long Zhu . Electrosynthesis of hydroxylamine from earth-abundant small molecules. Chinese Journal of Structural Chemistry, 2025, 44(1): 100383-100383. doi: 10.1016/j.cjsc.2024.100383
12. [12]
  Ali Dai , Zhiguo Zheng , Liusheng Duan , Jian Wu , Weiming Tan . Small molecule chemical scaffolds in plant growth regulators for the development of agrochemicals. Chinese Chemical Letters, 2025, 36(4): 110462-. doi: 10.1016/j.cclet.2024.110462
13. [13]
  Jun Xiong , Ke-Ke Chen , Neng-Bin Xie , Wei Chen , Wen-Xuan Shao , Tong-Tong Ji , Si-Yu Yu , Yu-Qi Feng , Bi-Feng Yuan . Demethylase-assisted site-specific detection of N¹-methyladenosine in RNA. Chinese Chemical Letters, 2024, 35(5): 108953-. doi: 10.1016/j.cclet.2023.108953
14. [14]
  Tian Feng , Yun-Ling Gao , Di Hu , Ke-Yu Yuan , Shu-Yi Gu , Yao-Hua Gu , Si-Yu Yu , Jun Xiong , Yu-Qi Feng , Jie Wang , Bi-Feng Yuan . Chronic sleep deprivation induces alterations in DNA and RNA modifications by liquid chromatography-mass spectrometry analysis. Chinese Chemical Letters, 2024, 35(8): 109259-. doi: 10.1016/j.cclet.2023.109259
15. [15]
  Yan Liu , Yang Wang , Jiayi Zhu , Xuxian Su , Xudong Lin , Liang Xu , Xiwen Xing . Employing pH-responsive RNA triplex to control CRISPR/Cas9-mediated gene manipulation in mammalian cells. Chinese Chemical Letters, 2024, 35(9): 109427-. doi: 10.1016/j.cclet.2023.109427
16. [16]
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17. [17]
  Xinyi Luo , Ke Wang , Yingying Xue , Xiaobao Cao , Jianhua Zhou , Jiasi Wang . Digital PCR-free technologies for absolute quantitation of nucleic acids at single-molecule level. Chinese Chemical Letters, 2025, 36(2): 109924-. doi: 10.1016/j.cclet.2024.109924
18. [18]
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19. [19]
  Aolei Tan , Xiaoxiao Ma . Exploring the functional roles of small-molecule metabolites in disease research: Recent advancements in metabolomics. Chinese Chemical Letters, 2024, 35(8): 109276-. doi: 10.1016/j.cclet.2023.109276
20. [20]
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