Citation: 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[J]. Chinese Chemical Letters, ;2026, 37(6): 111541. doi: 10.1016/j.cclet.2025.111541 shu

Aptamer-targeted and pH-responsive DNA tetrahedron for survivin mRNA fluorescence imaging and chemo/gene therapy

Mengyue Li ^{a, b} ,
Yue Zheng ^a ,
Zhijun Lu ^a ,
Yu Yang ^a ,
Jiangping Lei ^a ,
Yi Teng ^a ,
Wanyi Zhou ^a ,
Yiman Ge ^c ,
Chunhui Wu ^a ,
Hong Yang ^{a, *,} ,
Yiyao Liu ^{a, c, d, e, *,}

a.
Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, and School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610041, China
b.
Institute for Engineering Medicine, Kunming Medical University, Kunming 650500, China
c.
Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
d.
Traditional Chinese Medicine (TCM) Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
e.
Department of Urology, Deyang People's Hospital, Deyang 618099, China

yanghongyh@uestc.edu.cn

liuyiyao@uestc.edu.cn

Received Date: 10 April 2025
Revised Date: 30 June 2025
Accepted Date: 2 July 2025
Available Online: 6 July 2025

Figures(5)

In situ stimuli-responsive nanodevices have gained substantial attention in recent years owing to their remarkable potential to enhance tumor imaging and therapeutic effects. Herein, we formulated a pH-responsive, aptamer-functionalized DNA tetrahedral nanoplatform (ASTD) for improved visualization of survivin mRNA and chemo/gene therapy. ASTD, assembled by four single-stranded DNA, integrates pH-responsive i-motif sequences, survivin mRNA-targeted molecular beacons and AS1411 aptamers. Taking advantage of the tumor-targeting ability of AS1411 aptamer, ASTD monomers self-assemble into a multifunctional DNA polymeric tetrahedron (ASPD) on the tumor cell surface upon exposure to acidic tumor microenvironment. ASPD exhibits enhanced cellular uptake, superior survivin mRNA imaging, and efficient survivin gene silencing. Furthermore, Dox-loaded ASPD shows a significant antitumor effect, resulting in approximately 66% apoptosis of tumor cells. This study develops a dynamic DNA tetrahedral nanoplatform with diagnostic and therapeutic dual-functionalities, offering a promising strategy for advancing precise cancer theranostics.
- Dynamic DNA nanostructures,
- DNA tetrahedrons,
- Survivin mRNA imaging,
- Chemo/gene therapy,
- Targeted delivery
1. [1]
  R. Jia, Y. Wang, W. Ma, et al., Anal. Chem. 94 (2022) 5937–5945. doi: 10.1021/acs.analchem.2c00364
2. [2]
  M. Li, G. Yang, Y. Zheng, et al., J. Nanobiotechnology 21 (2023) 186. doi: 10.1111/nph.18701
3. [3]
  Y. Cai, X. Chen, J. Si, X. Mou, X. Dong, Small 17 (2021) e2103072. doi: 10.1002/smll.202103072
4. [4]
  Y. Hou, W. Bu, H. Ai, Z.R. Lu, T. Lammers, Adv. Healthc. Mater. 10 (2021) e2100243. doi: 10.1002/adhm.202100243
5. [5]
  G. Yang, M. Li, T. Song, et al., Adv. Healthc. Mater. 11 (2022) e2201615. doi: 10.1002/adhm.202201615
6. [6]
  L. Fan, X. Chong, M. Zhao, et al., Anal. Chem. 93 (2021) 665–670. doi: 10.1021/acs.analchem.0c04055
7. [7]
  Z. Chen, Y. Peng, X. Xie, et al., Theranostics 9 (2019) 5784–5796. doi: 10.7150/thno.36545
8. [8]
  J. Zheng, R. Yang, M. Shi, et al., Chem. Soc. Rev. 44 (2015) 3036–3055. doi: 10.1039/C5CS00020C
9. [9]
  N. Bidar, F. Oroojalian, B. Baradaran, et al., Trends Analyt. Chem. 131 (2020) 116021. doi: 10.1016/j.trac.2020.116021
10. [10]
  X. Wu, Y. Zhang, Y. Ding, et al., Adv. Sci. 12 (2025) e2414525. doi: 10.1002/advs.202414525
11. [11]
  T. Nie, Z. He, J. Zhu, L. Liu, Y. Chen, Adv. Ther. 3 (2020) 2000016. doi: 10.1002/adtp.202000016
12. [12]
  I. Nozaki, N. Ishikawa, Y. Miyanari, et al., Bioconjug. Chem. 33 (2022) 2149–2160. doi: 10.1021/acs.bioconjchem.2c00398
13. [13]
  X. Chen, N. Duan, C. Zhang, W. Zhang, J. Cancer. 7 (2016) 314–323. doi: 10.7150/jca.13332
14. [14]
  S.N. Brun, S.L. Markant, L.A. Esparza, et al., Oncogene 34 (2015) 3770–3779. doi: 10.1038/onc.2014.304
15. [15]
  X. Shen, Q. Ouyang, H. Tan, J. Ouyang, N. Na, Anal. Chem. 95 (2023) 5903–5910. doi: 10.1021/acs.analchem.2c04916
16. [16]
  Y. Yu, L. Zhang, Z. Qin, et al., Adv. Funct. Mater. 33 (2022) 2208797.
17. [17]
  H. Wei, F. Li, T. Xue, et al., Bioact. Mater. 28 (2023) 50–60.
18. [18]
  T. Nie, Z. He, Y. Zhou, et al., ACS Appl. Mater. Interfaces 11 (2019) 29593–29603. doi: 10.1021/acsami.9b10294
19. [19]
  M. Liu, L. Hao, D. Zhao, J. Li, Y. Lin, ACS Appl. Mater. Interfaces 14 (2022) 38506–38514. doi: 10.1021/acsami.2c09462
20. [20]
  T. Xu, S. Yu, Y. Sun, et al., Small 17 (2021) e2101780.
21. [21]
  M. Li, H. Zhang, P. Xiong, et al., J. Control. Release 379 (2025) 452–465. doi: 10.3390/machines13060452
22. [22]
  D. Xiao, Y. Li, T. Tian, et al., ACS Appl. Mater. Interfaces 13 (2021) 6109–6118. doi: 10.1021/acsami.0c23005
23. [23]
  Z. Cai, L. Bai, Q. Li, et al., ACS Nano 18 (2024) 35214–35229. doi: 10.1021/acsnano.4c08727
24. [24]
  L. Zhang, Y. Wang, J. Karges, et al., Adv. Mater. 35 (2023) e2210267. doi: 10.1002/adma.202210267
25. [25]
  W. Ma, Y. Yang, J. Zhu, et al., Adv. Mater. 34 (2022) e2109609.
26. [26]
  M. Zhang, Y. Wen, Z. Huang, et al., Chem. Eng. J. 454 (2023) 140399. doi: 10.1016/j.cej.2022.140399
27. [27]
  S. Li, T. Zeng, Z. Wu, et al., J. Am. Chem. Soc. 147 (2025) 2168–2181. doi: 10.1021/jacs.4c16438
28. [28]
  D. Xiao, T. Chen, T. Zhang, et al., Chin. Chem. Lett. 35 (2023) 108602.
29. [29]
  J. Wang, K. Wang, H. Peng, et al., Anal. Chem. 95 (2023) 4138–4146. doi: 10.1021/acs.analchem.2c05200
30. [30]
  H. Luo, Z. Wang, Q. Mo, et al., ACS Appl. Mater. Interfaces 15 (2023) 33223–33238. doi: 10.1021/acsami.3c01611
31. [31]
  T. Nie, Y. Fang, R. Zhang, et al., Bioact. Mater. 47 (2025) 51–63.
32. [32]
  M. Zeraati, D.B. Langley, P. Schofield, et al., Nat. Chem. 10 (2018) 631–637. doi: 10.1038/s41557-018-0046-3
33. [33]
  M. Debnath, K. Fatma, J. Dash, Angew. Chem. Int. Ed. 58 (2019) 2942–2957. doi: 10.1002/anie.201813288
34. [34]
  S. Tao, Y. Run, D. Monchaud, W. Zhang, Trend. Genet. 40 (2024) 853–867.
35. [35]
  W. Ma, B. Chen, S. Zou, et al., Anal. Chem. 91 (2019) 12538–12545. doi: 10.1021/acs.analchem.9b03420
1. [1]
  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
2. [2]
  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
3. [3]
  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
4. [4]
  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
5. [5]
  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
6. [6]
  Xiaohong Wen , Mei Yang , Lie Li , Mingmin Huang , Wei Cui , Suping Li , Haiyan Chen , Chen Li , Qiuping Guo . Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor. Chinese Chemical Letters, 2024, 35(8): 109291-. doi: 10.1016/j.cclet.2023.109291
7. [7]
  Jiaojiao Yang , Shaokun Yang , Wei Cheng , Jie Wu , Haijing Qu , Han Chen , Zhiran Duan , Yuqing Pan , Ning Wang , Chao Wang , Jian Gao , Bai Xiang , Xiangdong Xue . Self-assembled cyclodextrin-porphyrin nanoplatform for synergistic chemo-phototherapy and targeted delivery of camptothecin against breast cancer. Chinese Chemical Letters, 2026, 37(4): 111901-. doi: 10.1016/j.cclet.2025.111901
8. [8]
  Jiangshan Xu , Weifei Zhang , Zhengwen Cai , Yong Li , Long Bai , Shaojingya Gao , Qiang Sun , Yunfeng Lin . Tetrahedron DNA nanostructure/iron-based nanomaterials for combined tumor therapy. Chinese Chemical Letters, 2024, 35(11): 109620-. doi: 10.1016/j.cclet.2024.109620
9. [9]
  Chang Liu , Tao Wu , Lijiao Deng , Xuzi Li , Xin Fu , Shuzhen Liao , Wenjie Ma , Guoqiang Zou , Hai Yang . Programmed DNA walkers for biosensors. Chinese Chemical Letters, 2024, 35(9): 109307-. doi: 10.1016/j.cclet.2023.109307
10. [10]
  Fanghua Zhang , Yuyan Li , Hongyan Zhang , Wendong Liu , Zhe Hao , Mingzheng Shao , Ruizhong Zhang , Xiyan Li , Libing Zhang . Logically integrating exo/endogenous gated DNA trackers for precise microRNA imaging via synergistic manipulation. Chinese Chemical Letters, 2025, 36(1): 109848-. doi: 10.1016/j.cclet.2024.109848
11. [11]
  Hongmin Lei , Jie Zhou , Yichen Han , Yaqin Chai , Ruo Yuan . A periodically ordered cruciform DNA nanowire guided-localized HCR for simultaneous and rapid detection and imaging of dual-microRNAs. Chinese Chemical Letters, 2026, 37(6): 111737-. doi: 10.1016/j.cclet.2025.111737
12. [12]
  Du Liu , Yuyan Li , Hankun Zhang , Benhua Wang , Chaoyi Yao , Minhuan Lan , Zhanhong Yang , Xiangzhi Song . Three-in-one erlotinib-modified NIR photosensitizer for fluorescence imaging and synergistic chemo-photodynamic therapy. Chinese Chemical Letters, 2025, 36(2): 109910-. doi: 10.1016/j.cclet.2024.109910
13. [13]
  Leyuan Sun , Xiaoyu Xie , Fangfang Chen . 敦煌壁画的“DNA变身”. University Chemistry, 2025, 40(8): 211-217. doi: 10.12461/PKU.DXHX202410079
14. [14]
  Yongjian Jiang , Feng Cheng , Jun Zhou , Lei Zhan , Chunmei Li , Chengzhi Huang . Regulation of cancer cell apoptosis with DNA nanocalculator. Chinese Chemical Letters, 2026, 37(1): 110071-. doi: 10.1016/j.cclet.2024.110071
15. [15]
  Jia-Li Xie , Tian-Jin Xie , Yu-Jie Luo , Kai Mao , Cheng-Zhi Huang , Yuan-Fang Li , Shu-Jun Zhen . Octopus-like DNA nanostructure coupled with graphene oxide enhanced fluorescence anisotropy for hepatitis B virus DNA detection. Chinese Chemical Letters, 2024, 35(6): 109137-. doi: 10.1016/j.cclet.2023.109137
16. [16]
  Zhong Du , Li-Jun Zhu , Jia-Bao Xiong , Yu-Xiang Gao , Ya-Qi Cui , Maierhaba Aili , Chen-Yang Chu , Chi Zhang , Gao-Fei Huang , Xue-Liang Zhang , Nuernisha Alifu , Biao Dong . Multifunctional FA-PDA@ICG-Bi₂Se₃ nanoplatform for targeted NIR and X-ray dual-modal imaging and photothermal therapy of cervical cancer. Chinese Chemical Letters, 2026, 37(4): 111488-. doi: 10.1016/j.cclet.2025.111488
17. [17]
  Yang Qin , Jiangtian Li , Xuehao Zhang , Kaixuan Wan , Heao Zhang , Feiyang Huang , Limei Wang , Hongxun Wang , Longjie Li , Xianjin Xiao . Toeless and reversible DNA strand displacement based on Hoogsteen-bond triplex. Chinese Chemical Letters, 2024, 35(5): 108826-. doi: 10.1016/j.cclet.2023.108826
18. [18]
  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
19. [19]
  Zhongyu Wang , Lijun Wang , Huaixin Zhao . DNA-based nanosystems to generate reactive oxygen species for nanomedicine. Chinese Chemical Letters, 2024, 35(11): 109637-. doi: 10.1016/j.cclet.2024.109637
20. [20]
  Xiaolong Li , Changjiang Li , Chaopeng Shi , Jiarun Wang , Bei Yan , Xianjin Xiao , Tongbo Wu . CRISPR-Cas systems in DNA functional circuits: Strategies, challenges, prospects. Chinese Chemical Letters, 2025, 36(7): 110507-. doi: 10.1016/j.cclet.2024.110507

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(17)
HTML views(2)

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