Citation: 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[J]. Chinese Chemical Letters, ;2026, 37(9): 112031. doi: 10.1016/j.cclet.2025.112031 shu

Polycation-based miRNA delivery system for choroidal neovascularization treatment

Qiannan Cao ^{a, b, 1} ,
Yu Liang ^{c, 1} ,
Weiyi Xia ^{c, 1} ,
Anna Guo ^{a, b, 1} ,
Mingxia Jiang ^{a, b} ,
Lai Yang ^d ,
Qiaoyan Dong ^{a, b} ,
Wenming Zheng ^{a, b} ,
Yingli Yao ^{a, b} ,
Siting Zhang ^{a, b} ,
Huilin Yuan ^{a, b} ,
Pijun Su ^{a, b} ,
Rongmei Zhou ^c ,
Songyu Xu ^c ,
Bo Chen ^{a, *,} ,
Jing Yao ^{c, e, *,} ,
Huapan Fang ^{a, b, *,} ,
Huayu Tian ^a

a.
College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen 361005, China
b.
Shenzhen Research Institute of Xiamen University, Shenzhen 518000, China
c.
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China
d.
Department of Cardiology, Ezhou Hospital of Traditional Chinese Medicine, Ezhou 436000, China
e.
Department of Ophthalmology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830013, China

chenbo7892@xmu.edu.cn

yaojingxiao@163.com

hpfang@xmu.edu.cn

Received Date: 24 August 2025
Revised Date: 25 October 2025
Accepted Date: 27 October 2025
Available Online: 28 October 2025

Figures(3)

MicroRNA (miRNA)-based therapeutics hold great promise for the treatment of ocular fundus diseases. However, naked miRNAs exhibit poor stability in vivo, are readily degraded by nucleases in body fluids, and their negative charge hinders efficient uptake by target cells. Therefore, a safe and effective nucleic acid delivery system is essential. In this study, we developed an efficient and safe polycationic nucleic acid carrier by modifying polyethyleneimine (PEI) with p-toluenesulfonyl chloride (i.e., PEI-T₃). The introduction of tosyl groups onto PEI enhanced the hydrophobic interactions between polymer and cell membrane, and contributed to the cellular uptake of miRNA. Intravitreal injection of PEI-T₃/miRNA complexes caused negligible effects on retinal structure and function and did not induce neurotoxicity. Using microRNA-578 (miR-578) as the therapeutic gene, PEI-T₃/miR-578 treatment effectively downregulated the levels of vascular endothelial growth factor A (VEGF-A) and vascular cell adhesion molecule 1 (VCAM-1), suppressed the proliferation, migration, and tube formation of vascular endothelial cells. In a choroidal neovascularization (CNV) model, a single dose of PEI-T₃/miR-578 significantly relieved the disease progression and showed an excellent in vivo safety profile. This study provides a valuable reference for the in vivo delivery of miRNAs using polymeric carriers for the treatment of ocular fundus diseases.
- MicroRNA (miRNA)-based therapeutics,
- Polycationic nucleic acid carrier,
- Hydrophobic interactions,
- Disease progression,
- In vivo safety
1. [1]
  R.S. Apte, C.G. Solomon, N. Engl. J. Med. 385 (2021) 539–547. doi: 10.1056/nejmcp2102061
2. [2]
  P. Mitchell, G. Liew, B. Gopinath, T.Y. Wong, Lancet 392 (2018) 1147–1159. doi: 10.1016/S0140-6736(18)31550-2
3. [3]
  W.M. Amoaku, U. Chakravarthy, R. Gale, et al., Eye 29 (2015) 721–731. doi: 10.1038/eye.2015.48
4. [4]
  I.U. Scott, P.C. VanVeldhuisen, M.S. Ip, et al., J. Am. Med. Assoc. 317 (2017) 2072–2087. doi: 10.1001/jama.2017.4568
5. [5]
  J.A. Wells, A.R. Glassman, A.R. Ayala, et al., N. Engl. J. Med. 372 (2015) 1193–1203. doi: 10.1056/NEJMoa1414264
6. [6]
  N. Rayess, E. Rahimy, P. Storey, et al., Am. J. Ophthalmol. 165 (2016) 88–93. doi: 10.1016/j.ajo.2016.02.028
7. [7]
  S. Wang, D. Weissman, Y. Dong, Nat. Rev. Drug Discov. 24 (2025) 828–851. doi: 10.1038/s41573-025-01237-x
8. [8]
  Q. Tang, A. Khvorova, Nat. Rev. Drug Discov. 23 (2024) 341–364. doi: 10.1038/s41573-024-00912-9
9. [9]
  A. Mehta, D. Baltimore, Nat. Rev. Immunol. 16 (2016) 279–294. doi: 10.1038/nri.2016.40
10. [10]
  D.W. Penga, C.L. Lana, L.Q. Donga, et al., Proc. Natl. Acad. Sci. U. S. A. 119 (2022) e2204795119. doi: 10.1073/pnas.2204795119
11. [11]
  C.H. Liu, Y. Sun, J. Li, et al., Pro. Natl. Acad. Sci. U. S. A. 112 (2015) 12163–12168. doi: 10.1073/pnas.1508426112
12. [12]
  R.m. Zhou, L.j. Shi, K. Shan, et al., Theranostics 10 (2020) 3293–3307. doi: 10.7150/thno.39488
13. [13]
  J.B. Ulmer, U. Valley, R. Rappuoli, V. Nat. Biotechnology. 24 (2006) 1377–1383. doi: 10.1038/nbt1261
14. [14]
  M.S. Gebre, L.A. Brito, L.H. Tostanoski, et al., Cell 184 (2021) 1589–1603. doi: 10.1016/j.cell.2021.02.030
15. [15]
  K.A. Hajj, K.A. Whitehead, Nat. Rev. Mater. 2 (2017) 17056. doi: 10.1038/natrevmats.2017.56
16. [16]
  H. Fang, Y. Feng, J. Chen, H. Tian, X. Chen, Mater. Today Chem. 11 (2019) 269–282. doi: 10.1016/j.mtchem.2018.11.007
17. [17]
  H. Fang, Z. Guo, L. Lin, et al., J. Am. Chem. Soc. 30 (2018) 11992–12000. doi: 10.1021/jacs.8b05341
18. [18]
  H. Zhang, X. You, X. Wang, et al., Proc. Natl. Acad. Sci. U. S. A. 118 (2021) e2005191118. doi: 10.1073/pnas.2005191118
19. [19]
  Y. Sui, X. Hou, J. Zhang, et al., J. Mater. Chem. B 13 (2025) 10085–10117. doi: 10.1039/d5tb01556a
20. [20]
  H. Xu, J. Fan, J. Liu, et al., Chin. Chem. Lett. 36 (2025) 110833. doi: 10.1016/j.cclet.2025.110833
21. [21]
  X.Y. Guo, Z.Y. Yang, H.P. Fang, et al., Chin. J. Polym. Sci. 42 (2024) 1699–1709. doi: 10.1007/s10118-024-3171-z
22. [22]
  H. Fang, L. Lin, J. Chen, et al., Biomater. Sci. 7 (2019) 1716–1728. doi: 10.1039/c9bm00039a
23. [23]
  D. Xie, Q. Cao, H. Fang, Y. Li, H. Tian, Chin. Chem. Lett. 37 (2026) 111032. doi: 10.1016/j.cclet.2025.111032
24. [24]
  T. Nie, Z. He, J. Zhu, L. Liu, Y. Chen, Adv. Ther. 3 (2020) 2000016. doi: 10.1002/adtp.202000016
25. [25]
  T. Nie, Z. He, Y. Zhou, et al., ACS Appl. Mater. Interfaces 11 (2019) 29593–29603. doi: 10.1021/acsami.9b10294
26. [26]
  S. Zhang, H. Fang, H. Tian, Biomacromolecules 25 (2024) 7015–7057. doi: 10.1021/acs.biomac.4c01193
27. [27]
  M. Jiang, H. Fang, H. Tian, J. Control. Release 380 (2025) 138–174. doi: 10.1016/j.jconrel.2025.01.063
28. [28]
  W. Xiao, F. Wang, Y. Gu, et al., Chin. Chem. Lett. 35 (2024) 108755. doi: 10.1016/j.cclet.2023.108755
29. [29]
  S. Ding, E. Alexander, H. Liang, et al., Chem. Rev. 125 (2025) 4009–4068. doi: 10.1021/acs.chemrev.4c00482
30. [30]
  H. Fang, Z. Guo, J. Chen, et al., Nat. Commun. 12 (2021) 6742. doi: 10.1038/s41467-021-27078-x
31. [31]
  R. Rupaimoole, F.J. Slack, Nat. Rev. Drug Discov. 16 (2017) 203–222. doi: 10.1038/nrd.2016.246
32. [32]
  J.K. Cheong, Y.C. Tang, L. Zhou, H. Cheng, H.P. Too, Curr. Opin. Biotechnol. 74 (2022) 256–262. doi: 10.1016/j.copbio.2021.12.007
33. [33]
  Z. Fang, X. Zhang, H. Huang, J. Wu, Chin. Chem. Lett. 33 (2022) 1693–1704. doi: 10.1016/j.cclet.2021.11.050
34. [34]
  C. Diener, A. Keller, E. Meese, Trends Genet. 38 (2022) 613–626. doi: 10.1016/j.tig.2022.02.006
35. [35]
  A. Jeyaram, T.N. Lamichhane, S. Wang, et al., Mol. Ther. 28 (2020) 975–985. doi: 10.1016/j.ymthe.2019.12.007
36. [36]
  S. Dong, H. Fang, J. Zhu, et al., ACS Nano 19 (2025) 2742–2758. doi: 10.1021/acsnano.4c15130
37. [37]
  H. Fang, Y. Wu, L. Chen, et al., ACS Nano 17 (2023) 4748–4763. doi: 10.1021/acsnano.2c11159
38. [38]
  D. Jana, Z. Han, X. Huang, et al., ACS Nano 18 (2024) 16674–16683. doi: 10.1021/acsnano.4c01640
39. [39]
  R. De, M.K. Mahata, K.T. Kim, Adv. Sci. 9 (2022) 2105373. doi: 10.1002/advs.202105373
40. [40]
  J. Song, Y.K. Kim, Mol. Ther. Nucl. Acids 24 (2021) 284–293. doi: 10.1016/j.omtn.2021.02.031
41. [41]
  M. Shyam, S. Sidharth, A. Veronica, et al., Mol. Biol. Rep. 52 (2025) 380. doi: 10.1007/s11033-025-10490-7
42. [42]
  Y. Liu, J. Shen, S.D. Fortmann, J. Wang, D. Vestweber, P.A. Campochiaro, JCI Insight 2 (2017) e95530. doi: 10.1172/jci.insight.95530
43. [43]
  W. Deng, C. Yi, W. Pan, et al., Immunity Ageing 20 (2023) 65. doi: 10.1186/s12979-023-00389-x
1. [1]
  Lihang Wang , Mary Li Javier , Chunshan Luo , Tingsheng Lu , Shudan Yao , Bing Qiu , Yun Wang , Yunfeng Lin . Research advances of tetrahedral framework nucleic acid-based systems in biomedicine. Chinese Chemical Letters, 2024, 35(11): 109591-. doi: 10.1016/j.cclet.2024.109591
2. [2]
  Wei Yan , Naizhen Zhang , Xiao Liu , Qiyu He , Xucheng Lv , Jianghui Sun , Lili Zhuang , Yuexin Zou , Yajie Zhang , Yuhang Liang , Yanjie Wang , Siyuan Li , Yonghui Sun . Development of visible-light photocaged molecular glues (vc-MGs) for B-cell malignancies therapy with improved safety and pharmacokinetic profiles in vivo. Chinese Chemical Letters, 2026, 37(5): 112064-. doi: 10.1016/j.cclet.2025.112064
3. [3]
  Zerong Pei , Suyun Hu , Huimin Wei , Liqin Ding , Jingbo Liu , Fengyun Li , Hongyu Chen . Multifunctional carrier-free nanodrugs for enhanced delivery and efficacy of hydrophobic antitumor drugs. Chinese Chemical Letters, 2026, 37(1): 110981-. doi: 10.1016/j.cclet.2025.110981
4. [4]
  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. Chinese Chemical Letters, 2025, 36(8): 110614-. doi: 10.1016/j.cclet.2024.110614
5. [5]
  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
6. [6]
  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
7. [7]
  Yunxia Liu , Guandong Wu , Lin Li , Yiming Niu , Bingsen Zhang , Botao Qiao , Junhu Wang . Construction of sintering-resistant gold catalysts via ascorbic-acid inducing strong metal-support interactions. Chinese Chemical Letters, 2025, 36(4): 110608-. doi: 10.1016/j.cclet.2024.110608
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]
  Jialin Guo , Mingrui Gu , Yahui Chen , Tao Xiong , Yiyang Zhang , Simin Chen , Mingle Li , Xiaoqiang Chen , Xiaojun Peng . Nucleic acid delivery by lipid nanoparticles for organ targeting. Chinese Chemical Letters, 2025, 36(11): 110849-. doi: 10.1016/j.cclet.2025.110849
10. [10]
  Jiajia Lv , Jie Gao , Hongyu Li , Zeli Yuan , Nan Dong . Rational design of hydroxytricyanopyrrole-based probes with high affinity and rapid visualization for amyloid-β aggregates in vitro and in vivo. Chinese Chemical Letters, 2024, 35(5): 108940-. doi: 10.1016/j.cclet.2023.108940
11. [11]
  Kun Shang , Yinghua Lv , Yibo Yang , Senyu Yang , Zelong Chen , Ke Yang , Cong Li , Shuang Chao , Yuchao Lu , Yuxin Pei , Zhichao Pei . "Dual sweet" supramolecular glycosyl-nanoproteins based on carbohydrate-protein interaction for targeted drug delivery in vivo. Chinese Chemical Letters, 2026, 37(7): 111798-. doi: 10.1016/j.cclet.2025.111798
12. [12]
  Bingbing Shi , Yuchun Wang , Yi Zhou , Xing-Xing Zhao , Yizhou Li , Nuoqian Yan , Wen-Juan Qu , Qi Lin , Tai-Bao Wei . A supramolecular oligo[2]rotaxane constructed by orthogonal platinum(Ⅱ) metallacycle and pillar[5]arene-based host–guest interactions. Chinese Chemical Letters, 2024, 35(10): 109540-. doi: 10.1016/j.cclet.2024.109540
13. [13]
  Xueru Zhao , Aopu Wang , Shimin Wang , Zhijie Song , Li Ma , Li Shao . Adsorption and visual detection of nitro explosives by pillar[n]arenes-based host–guest interactions. Chinese Chemical Letters, 2025, 36(4): 110205-. doi: 10.1016/j.cclet.2024.110205
14. [14]
  Zhe-Han Yang , Jie Yin , Lei Xin , Yuanfang Li , Yijie Huang , Ruo Yuan , Ying Zhuo . Research advancement of DNA-based intelligent hydrogels: Manufacture, characteristics, application of disease diagnosis and treatment. Chinese Chemical Letters, 2024, 35(10): 109558-. doi: 10.1016/j.cclet.2024.109558
15. [15]
  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
16. [16]
  Zixu Xie , Pengfei Zhang , Ziyao Zhang , Chen Chen , Xing Wang . The choice of antimicrobial polymers: Hydrophilic or hydrophobic?. Chinese Chemical Letters, 2024, 35(9): 109768-. doi: 10.1016/j.cclet.2024.109768
17. [17]
  Jin Long , Xingqun Zheng , Bin Wang , Chenzhong Wu , Qingmei Wang , Lishan Peng . Improving the electrocatalytic performances of Pt-based catalysts for oxygen reduction reaction via strong interactions with single-CoN₄-rich carbon support. Chinese Chemical Letters, 2024, 35(5): 109354-. doi: 10.1016/j.cclet.2023.109354
18. [18]
  Pu Zhang , Xiang Mao , Xuehua Dong , Ling Huang , Liling Cao , Daojiang Gao , Guohong Zou . Two UV organic-inorganic hybrid antimony-based materials with superior optical performance derived from cation-anion synergetic interactions. Chinese Chemical Letters, 2024, 35(9): 109235-. doi: 10.1016/j.cclet.2023.109235
19. [19]
  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
20. [20]
  Yihao He , Ru Guo , Lu Yang , Ling Li , Tong Zhang , Bing Wang , Yongzhuo Huang . Phospholipid complex-based microemulsion for treating concurrence of primary sclerosing cholangitis and inflammatory bowel disease via gut-liver crosstalk. Chinese Chemical Letters, 2025, 36(10): 110778-. doi: 10.1016/j.cclet.2024.110778

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