Application and research progress of tetrahedral framework nucleic acids in the field of medicine

doi:10.3969/j.issn.1674-8115.2023.03.015

Abstract

Abstract:

Since the first proposal by Seeman in 1982, DNA nanostructures have been gradually improved, and have been widely developed and applied to the field of biomedical fields. In recent years, as a representative of 3D DNA nanostructures, tetrahedral framework nucleic acids (tFNA) has made certain research progress and has good application prospects in frontier fields such as biosensors, tumor therapy, antigen detection, regenerative medicine, with the advantages of their good biocompatibility, editability, high stability and easy preparation. This paper briefly describes the concepts of tFNA, and summarizes the applications and research progress of tFNA in the following fields from the perspective of therapeutic applications: ① Building novel self-assembled complexes to improve the efficacy of free drugs, carrying small RNA molecules to slow down tumor progression, and self-assembled complexes for targeted therapy, etc, as biological vectors and tumor drug delivery. ② Regulating inflammation and immune response, such as reducing the level of inflammatory factors, treating inflammatory diseases, preventing diabetes, and acting as immunomodulators, etc. ③ Enhancing tissue regeneration, such as promoting stem cell proliferation and differentiation, stimulating peripheral nerve regeneration, and facilitating wound repair through angiogenesis. This review summarizes the research progress of tFNA, and looks forward to its application prospects based on the analysis of the shortcomings of existing research, in order to provide reference for further research.

Key words: tetrahedral framework nucleic acid (tFNA), biological vector, tumor, inflammation, immune response, tissue regeneration, wound repair

CLC Number:

XIE Shasha, LÜ Yehui, LIN Jian. Application and research progress of tetrahedral framework nucleic acids in the field of medicine[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 380-384.

Figures/Tables 2

TrendMD

References 26

1	SEEMAN N C. Nucleic acid junctions and lattices[J]. J Theor Biol, 1982, 99(2): 237-247.
2	GOODMAN R P, SCHAAP I A, TARDIN C F, et al. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication[J]. Science, 2005, 310(5754): 1661-1665.
3	ZHANG T, CUI W T, TIAN T R, et al. Progress in biomedical applications of tetrahedral framework nucleic acid-based functional systems[J]. ACS Appl Mater Interfaces, 2020, 12(42): 47115-47126.
4	ZHANG X L, LIU N X, ZHOU M, et al. The application of tetrahedral framework nucleic acids as a drug carrier in biomedicine fields[J]. Curr Stem Cell Res Ther, 2021, 16(1): 48-56.
5	叶德楷, 左小磊, 樊春海. 基于DNA纳米结构的传感界面调控及生物检测应用[J]. 化学进展, 2017, 29(1): 36-46.
	YE D K, ZUO X L, FAN C M. DNA nanostructure-based engineering of the biosensing interface for biomolecular detection [J]. Progress in Chemistry, 2017, 29(1): 36-46.
6	SUN Y, LIU Y H, ZHANG B W, et al. Erythromycin loaded by tetrahedral framework nucleic acids are more antimicrobial sensitive against Escherichia coli (E. coli)[J]. Bioact Mater, 2021, 6(8): 2281-2290.
7	ZHANG M, ZHANG X L, TIAN T R, et al. Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis[J]. Bioact Mater, 2022, 8: 368-380.
8	AIUTI A, BIASCO L, SCARAMUZZA S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome[J]. Science, 2013, 341(6148): 1233151.
9	SONG G Q, DONG H S, MA D H, et al. Tetrahedral framework nucleic acid delivered RNA therapeutics significantly attenuate pancreatic cancer progression via inhibition of CTR1-dependent copper absorption[J]. ACS Appl Mater Interfaces, 2021, 13(39): 46334-46342.
10	CHAROENPHOL P, BERMUDEZ H. Aptamer-targeted DNA nanostructures for therapeutic delivery[J]. Mol Pharm, 2014, 11(5): 1721-1725.
11	XIE X, SHAO X, MA W, et al. Overcoming drug-resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures[J]. Nanoscale, 2018, 10(12): 5457-5465.
12	MA W J, ZHAN Y X, ZHANG Y X, et al. An intelligent DNA nanorobot with in vitro enhanced protein lysosomal degradation of HER2[J]. Nano Lett, 2019, 19(7): 4505-4517.
13	ZHANG T, TIAN T R, ZHOU R H, et al. Design, fabrication and applications of tetrahedral DNA nanostructure-based multifunctional complexes in drug delivery and biomedical treatment[J]. Nat Protoc, 2020, 15(8): 2728-2757.
14	QIAN H S, ZHOU T, FU Y X, et al. Self-assembled tetrahedral framework nucleic acid mediates tumor-associated macrophage reprogramming and restores antitumor immunity[J]. Mol Ther Nucleic Acids, 2022, 27: 763-773.
15	WANG Y, LI Y J, GAO S, et al. Tetrahedral framework nucleic acids can alleviate taurocholate-induced severe acute pancreatitis and its subsequent multiorgan injury in mice[J]. Nano Lett, 2022, 22(4): 1759-1768.
16	ZHOU M, GAO S, ZHANG X L, et al. The protective effect of tetrahedral framework nucleic acids on periodontium under inflammatory conditions[J]. Bioact Mater, 2020, 6(6): 1676-1688.
17	GAO S, ZHOU M, LI Y J, et al. Tetrahedral framework nucleic acids reverse new-onset type 1 diabetes[J]. ACS Appl Mater Interfaces, 2021, 13(43): 50802-50811.
18	LI Y J, GAO S, SHI S R, et al. Tetrahedral framework nucleic acid-based delivery of resveratrol alleviates insulin resistance: from innate to adaptive immunity[J]. Nanomicro Lett, 2021, 13(1): 86.
19	LIU X Y, YU Z Y, WU Y, et al. The immune regulatory effects of tetrahedral framework nucleic acid on human T cells via the mitogen-activated protein kinase pathway[J]. Cell Prolif, 2021, 54(8): e13084.
20	ZHONG J, GUO B, XIE J, et al. Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter[J]. Bone Res, 2016, 4: 15036.
21	LI P, FU L, LIAO Z, et al. Chitosan hydrogel/3D-printed poly(ε-caprolactone) hybrid scaffold containing synovial mesenchymal stem cells for cartilage regeneration based on tetrahedral framework nucleic acid recruitment[J]. Biomaterials, 2021, 278: 121131.
22	FU L W, LI P X, ZHU J Y, et al. Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ[J]. Bioact Mater, 2022, 9: 411-427.
23	YAO Y X, WEN Y T, LI Y J, et al. Tetrahedral framework nucleic acids facilitate neurorestoration of facial nerves by activating the NGF/PI3K/AKT pathway[J]. Nanoscale, 2021, 13(37): 15598-15610.
24	LIN S Y, ZHANG Q, LI S H, et al. Antioxidative and angiogenesis-promoting effects of tetrahedral framework nucleic acids in diabetic wound healing with activation of the Akt/Nrf2/HO-1 pathway[J]. ACS Appl Mater Interfaces, 2020, 12(10): 11397-11408.
25	ZHAO D, LIU M T, LI J J, et al. Angiogenic aptamer-modified tetrahedral framework nucleic acid promotes angiogenesis in vitro and in vivo[J]. ACS Appl Mater Interfaces, 2021, 13(25): 29439-29449.
26	GUAN H Q, YANG S L, ZHENG C, et al. DNAzyme-based sensing probe protected by DNA tetrahedron from nuclease degradation for the detection of lead ions[J]. Talanta, 2021, 233: 122543.

Application direction	Advantage	Shortcoming
Protecting probes from enzymatic degradation^[26]	Good biocompatibility, editability, high stability and ease of preparation^[5]	Biological stability, maximum load and structural controllability still need to be improved
Being as biological vectors; tumor drug delivery for precise targeting therapy^[9-13]	Targeted action, enhanced drug stability and uptake efficiency^[6-7]	Biosafety to be verified; lack of systematic research on long-term impacts
Treating inflammatory diseases, acting as immunomodulators^[15-19]	Regulating inflammation and immune response^[15-19]	Most of them are animal experiments, and the effect on human beings is yet to be proved
Promoting tissue regeneration^[23-25]	Promoting stem cell proliferation and differentiation and migration^[23-25]	The specific mechanisms of interaction with molecules and organisms are less studied.

Application direction	Advantage	Shortcoming
Protecting probes from enzymatic degradation^[26]	Good biocompatibility, editability, high stability and ease of preparation^[5]	Biological stability, maximum load and structural controllability still need to be improved
Being as biological vectors; tumor drug delivery for precise targeting therapy^[9-13]	Targeted action, enhanced drug stability and uptake efficiency^[6-7]	Biosafety to be verified; lack of systematic research on long-term impacts
Treating inflammatory diseases, acting as immunomodulators^[15-19]	Regulating inflammation and immune response^[15-19]	Most of them are animal experiments, and the effect on human beings is yet to be proved
Promoting tissue regeneration^[23-25]	Promoting stem cell proliferation and differentiation and migration^[23-25]	The specific mechanisms of interaction with molecules and organisms are less studied.

[1]	FU Xiaohan, WANG Juan, CUI Wenguo, WANG Yan. Effect of high hydrophilic electrospun short fibrous sponge on wound repair [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 269-277.
[2]	WU Zhaoyu, XU Zhijue, PU Hongji, WANG Xin, LU Xinwu. Physiological function of nerve injury-induced protein 1 and its role in relevant diseases [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 358-364.
[3]	GE Lingling, HUANG Hongjun, LUO Yan. Research progress in the role and mechanism of lactylation in diseases [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 374-379.
[4]	WU Bing, LI Xiaomin, LIU Siyu, ZHAO Lulu, WU Wen, HAO Yongqiang, AI Songtao. Preliminary application of improved 3D printed pathological section box to assisting stitching pathological images of bone tumor [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 180-187.
[5]	GUO Liqiang, ZHAO Shitian, SHU Bing. Research progress in the roles of Notch signaling pathway during fracture healing [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 222-229.
[6]	WU Zhenkai, DENG Bo, PAN Yu, DING Feng. Research progress in the role and mechanism of acyloxyacyl hydrolase in diseases [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(1): 101-107.
[7]	XIE Xiaolei, JIANG Peixin, ZHANG Jinghong, MO Junjian, WU Kefan, ZENG Kangyi. A review of RIZ1 regulation of the signal pathways in obesity and tumors [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(1): 114-119.
[8]	MA Fangfang, QIN Jiejie, REN Lingjie, TANG Xiaomei, LIU Jia, SHI Minmin, JIANG Lingxi. Establishment of a 3D culture model in vitro of pancreatic cancer primary cells using hydrogel microspheres [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(1): 79-87.
[9]	CUI Xiwei, CHUNG Manhon, AIMAIER Rehanguli, WANG Zhichao, LI Qingfeng. Role of human pleiotrophin in the metastasis of malignant peripheral nerve sheath tumor [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(9): 1225-1238.
[10]	CHU Yunkai, LIAO Chunhua, DENG Huayun, HUANG Lei. Study of the regulatory network of MUC1 and tumor-associated proteins [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1024-1033.
[11]	QIU Jiahui, CAI Qianqian, YANG Yan, CHENG Feichi, QIU Zhengjun, HUANG Chen. Value of combined perineural lymphovascular invasion and tumor-stroma ratio in guiding the prognosis of colorecatal cancer [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1070-1080.
[12]	LIN Jiayu, QIN Jiejie, JIANG Lingxi. Progress in metabolism of the immune cells in tumor microenvironment [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1122-1130.
[13]	A Tingxi, SHAO Chunyi, FU Yao. Research progress on the role of regulatory T cells in ocular surface diseases [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1145-1150.
[14]	LIU Hongqiang, LU Yanqing, GAO Yuxuan, WANG Yiyun, WANG Chuandong, ZHANG Xiaoling. Construction of OPEI vector for silencing TRAF6 to promote cartilage regeneration in inflammatory environment [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(7): 846-857.
[15]	WANG Yuxin, SUN Ruiqi, LIU Jianhua, HE Weina. Development of pH-responsive fluorescent probe for tumor microenvironment imaging [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(7): 875-884.