Citation: Tingting Zuo, Tao He, Yuan Gao, Siyi Yang, Yun Wang, Zhengyang Yang, Chao Zhang, Yunfeng Lin. Engineered tetrahedral framework nucleic acids (tFNAs): Modification strategies and biomedical applications[J]. Chinese Chemical Letters, ;2026, 37(10): 112102. doi: 10.1016/j.cclet.2025.112102 shu

Engineered tetrahedral framework nucleic acids (tFNAs): Modification strategies and biomedical applications

Tingting Zuo ^{a, 1} ,
Tao He ^{b, 1} ,
Yuan Gao ^c ,
Siyi Yang ^b ,
Yun Wang ^b ,
Zhengyang Yang ^{d, *,} ,
Chao Zhang ^{e, *,} ,
Yunfeng Lin ^{b, *,}

a.
College of Biological Sciences and Technology, Yili Normal University, Xinjiang Key Laboratory of Lavender Conservation and Utilization, Yining 835000, China
b.
State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Centre for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
c.
Department of Gastroenterology and Hepatology, Digestive Endoscopy Medical Engineering Research Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China
d.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
e.
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China

doctoryangzy@163.com

zc15996256330@smu.edu.cn

yunfenglin@scu.edu.cn

Received Date: 25 July 2025
Revised Date: 10 November 2025
Accepted Date: 11 November 2025
Available Online: 12 November 2025

Figures(1)

Tetrahedral framework nucleic acids (tFNAs) have emerged as a promising platform for a wide range of biomedical applications due to their unique structural stability, ease of synthesis, and excellent biocompatibility. This review provides a comprehensive overview of the various modification strategies for tFNAs, including vertex modification, edge functional loading, internal encapsulation, and surface coating. These modifications enable precise control over their biological activity, facilitating advancements in drug delivery, gene therapy, tissue engineering, and diagnostic imaging. Additionally, the structural engineering of tFNAs has enabled their integration into theranostic platforms, offering significant potential for personalized medicine. The review also discusses the challenges involved in the clinical translation of tFNAs, such as scalability, pharmacokinetic optimization, and regulatory approval, and presents a forward-looking perspective on the emerging trends that could further broaden the scope of tFNAs in clinical applications. Finally, we conclude by outlining the future prospects of tFNAs in next-generation therapeutic and diagnostic systems, highlighting their transformative potential in the biomedical field.
- Tetrahedral framework nucleic acids,
- DNA nanotechnology,
- Functionalization strategies,
- Biomedical applications,
- Therapeutics,
- Diagnostics
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