适配体筛选技术及其在肿瘤治疗中的研究进展

国际肿瘤学杂志››2025,Vol. 52››Issue (5): 304-308.doi:10.3760/cma.j.cn371439-20240920-00051

适配体筛选技术及其在肿瘤治疗中的研究进展

郑思齐¹, 郭婷¹, 王敬¹, 田映红²(), 张兴梅¹()

¹南方医科大学基础医学院神经生物学教研室，广州 510515
²南方医科大学基础医学院实验管理中心，广州 510515

收稿日期:2024-09-20修回日期:2024-11-08出版日期:2025-05-08发布日期:2025-06-24
通讯作者:田映红,张兴梅 E-mail:510918051@qq.com;zxmray@hotmail.com
基金资助:
国家自然科学基金(82371480);国家自然科学基金(82073340);广东省基础与应用基础研究基金(2023A1515011148);广东省基础与应用基础研究基金(2024A1515013046);广东省医学科研基金(A2023432)

Advances in aptamers screening and the applications in cancer therapy

Zheng Siqi¹, Guo Ting¹, Wang Jing¹, Tian Yinghong²(), Zhang Xingmei¹()

¹Department of Neurobiology， School of Basic Medical Sciences， Southern Medical University， Guangzhou 510515， China
²Experiment Teaching & Administration Center， School of Basic Medical Sciences， Southern Medical University， Guangzhou 510515， China

Received:2024-09-20Revised:2024-11-08Online:2025-05-08Published:2025-06-24
Contact:Tian Yinghong, Zhang Xingmei E-mail:510918051@qq.com;zxmray@hotmail.com
Supported by:
National Natural Science Foundation of China(82371480);National Natural Science Foundation of China(82073340);Guangdong Basic and Applied Basic Research Foundation(2023A1515011148);Guangdong Basic and Applied Basic Research Foundation(2024A1515013046);Medical Scientific Research Foundation of Guangdong Province of China(A2023432)

摘要/Abstract

摘要：

适配体是一类能与靶标分子高亲和特异性结合的短DNA/RNA单链寡核苷酸，具有高亲和特异性、相对分子质量小、低免疫原性等优点，已经被广泛应用于生物医学研究、临床诊断与治疗、生物传感器开发等领域。指数级富集配体系统进化技术（SELEX）是一种体外筛选技术，通过多轮循环筛选，富集与靶标高亲和特异性结合的适配体，在肿瘤治疗中具有广泛的应用。

关键词:适配体,SELEX适体技术,肿瘤治疗方案

Abstract:

Aptamers are a class of short DNA/RNA single strand oligonucleotides that can bind to target molecules with high affinity specificity. They have the advantages of high affinity specificity， low molecular weight and low immunogenicity， and have been widely used in biomedical research， clinical diagnosis and therapy， and biosensor development. Systematic evolution of ligand by exponential enrichment （SELEX） is anin vitroscreening technique， which enriches the aptamers with high affinity and specific binding to the target through multiple cycles of screening， and has a wide range of applications in tumor therapy.

Key words:Aptamer,SELEX aptamer technique,Antineoplastic protocols

郑思齐, 郭婷, 王敬, 田映红, 张兴梅. 适配体筛选技术及其在肿瘤治疗中的研究进展[J]. 国际肿瘤学杂志, 2025, 52(5): 304-308.

Zheng Siqi, Guo Ting, Wang Jing, Tian Yinghong, Zhang Xingmei. Advances in aptamers screening and the applications in cancer therapy[J]. Journal of International Oncology, 2025, 52(5): 304-308.

参考文献39

[1]	Qian S, Chang D, He S, et al. Aptamers from random sequence space: accomplishments, gaps and future considerations[J].Anal Chim Acta,2022,1196: 339511. DOI:10.1016/j.aca.2022.339511.
[2]	Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands[J].Nature,1990,346(6287): 818-822. DOI:10.1038/346818a0.
[3]	Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase[J].Science,1990,249(4968): 505-510. DOI:10.1126/science.2200121. pmid:2200121
[4]	Wu L, Zhang Y, Wang Z, et al. Aptamer-based cancer cell analysis and treatment[J].ChemistryOpen,2022,11(10): e202200141. DOI:10.1002/open.202200141.
[5]	Zhang Y, Lai BS, Juhas M. Recent advances in aptamer discovery and applications[J].Molecules,2019,24(5): 941. DOI:10.3390/molecules24050941.
[6]	Zhu C, Feng Z, Qin H, et al. Recent progress of SELEX methods for screening nucleic acid aptamers[J].Talanta,2024,266(Pt 1): 124998. DOI:10.1016/j.talanta.2023.124998.
[7]	Lyu C, Khan IM, Wang Z. Capture-SELEX for aptamer selection: a short review[J].Talanta,2021,229: 122274. DOI:10.1016/j.talanta.2021.122274.
[8]	Zhu C, Yang G, Ghulam M, et al. Evolution of multi-functional capillary electrophoresis for high-efficiency selection of aptamers[J].Biotechnol Adv,2019,37(8): 107432. DOI:10.1016/j.biotechadv. 2019.107432.
[9]	Jing M, Bowser MT. Isolation of DNA aptamers using micro free flow electrophoresis[J].Lab Chip,2011,11(21): 3703-3709. DOI:10.1039/c1lc20461k. pmid:21947169
[10]	Li Y, Tam WW, Yu Y, et al. The application of aptamer in biomarker discovery[J].Biomark Res,2023,11(1): 70. DOI:10. 1186/s40364-023-00510-8.
[11]	Sun X, Xie L, Qiu S, et al. Elucidation of CKAP4-remodeled cell mechanics in driving metastasis of bladder cancer through aptamer-based target discovery[J].Proc Natl Acad Sci U S A,2022,119(16): e2110500119. DOI:10.1073/pnas.2110500119.
[12]	Yu F, Chen J, Wang Z, et al. Screening aptamers for serine β- lactamase-expressing bacteria with precision-SELEX[J].Talanta,2021,224: 121750. DOI:10.1016/j.talanta.2020.121750.
[13]	Nikam PS, Palachandra S, Kingston JJ. In vitro selection and characterization of ssDNA aptamers by cross-over SELEX and its application for detection of S. Typhimurium[J].Anal Biochem,2022,656: 114884. DOI:10.1016/j.ab.2022.114884.
[14]	Duan Y, Zhang C, Wang Y, et al. Research progress of whole-cell-SELEX selection and the application of cell-targeting aptamer[J].Mol Biol Rep,2022,49(8): 7979-7993. DOI:10.1007/s11033-022-07317-0. pmid:35274201
[15]	Wen K, Chen Y, Meng X, et al. A microfluidic dual-aptamer sandwich assay for rapid and cost-effective detection of recombinant proteins[J].Microchem J,2023,188: 108454. DOI:10.1016/j.microc.2023.108454.
[16]	Chang D, Wang Z, Flynn CD, et al. A high-dimensional microfluidic approach for selection of aptamers with programmable binding affinities[J].Nat Chem,2023,15(6): 773-780. DOI:10.1038/s41557-023-01207-z. pmid:37277648
[17]	Qiao N, Li J, Wu X, et al. Speeding up in vitro discovery of structure-switching aptamers via magnetic cross-linking precipitation[J].Anal Chem,2019,91(21): 13383-13389. DOI:10.1021/acs.analchem.9b00081. pmid:31580650
[18]	Liu J, Duan Q, Shao Z, et al. Formaldehyde cross-linking-assisted phase separation for protein aptamer selection[J].Anal Chem,2023,95(16): 6700-6708. DOI:10.1021/acs.analchem.3c00434. pmid:37052573
[19]	Komarova N, Barkova D, Kuznetsov A. Implementation of high-throughput sequencing (HTS) in aptamer selection technology[J].Int J Mol Sci,2020,21(22): 8774. DOI:10.3390/ijms21228774.
[20]	Guo L, Song Y, Yuan Y, et al. Identification of nucleic acid aptamers against lactate dehydrogenase via SELEX and high-throughput sequencing[J].Anal Bioanal Chem,2021,413(17): 4427-4439. DOI:10.1007/s00216-021-03397-2. pmid:34028561
[21]	Ferreira D, Barbosa J, Sousa DA, et al. Selection of aptamers against triple negative breast cancer cells using high throughput sequencing[J].Sci Rep,2021,11(1): 8614. DOI:10.1038/s41598-021-87998-y.
[22]	Yazdian-Robati R, Bayat P, Oroojalian F, et al. Therapeutic applications of AS1411 aptamer, an update review[J].Int J Biol Macromol,2020,155: 1420-1431. DOI:10.1016/j.ijbiomac.2019.11.118. pmid:31734366
[23]	Mehrnia SS, Hashemi B, Mowla SJ, et al. Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles[J].Radiat Oncol,2021,16(1): 33. DOI:10.1186/s13014-021-01751-3.
[24]	Huang BT, Lai WY, Yeh CL, et al. AptBCis1, an aptamer-cisplatin conjugate, is effective in lung cancer leptomeningeal carcinomatosis[J].ACS Nano,2024,18(41): 27905-27916. DOI:10.1021/acsnano.4c04680.
[25]	Donne R, Lujambio A. The liver cancer immune microenvironment: therapeutic implications for hepatocellular carcinoma[J].Hepatology,2023,77(5): 1773-1796. DOI:10.1002/hep.32740.
[26]	Wang Z, Wu C, Liu J, et al. Aptamer-mediated hollow MnO₂for targeting the delivery of sorafenib[J].Drug Deliv,2023,30(1): 28-39. DOI:10.1080/10717544.2022.2149897.
[27]	Zhang Y, Bi J, Huang J, et al. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications[J].Int J Nanomedicine,2020,15: 6917-6934. DOI:10.2147/ijn.S264498.
[28]	张渊, 白芷玉, 李琪, 等. 外泌体在恶性肿瘤中的研究现状[J].国际肿瘤学杂志,2023,50(8): 484-488. DOI:10.3760/cma.j.cn371439-20230315-00092.
[29]	Han Q, Xie QR, Li F, et al. Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer[J].Theranostics,2021,11(13): 6526-6541. DOI:10. 7150/thno.53886. pmid:33995674
[30]	Tran PHL, Wang T, Yin W, et al. Aspirin-loaded nanoexosomes as cancer therapeutics[J].Int J Pharm,2019,572: 118786. DOI:10.1016/j.ijpharm.2019.118786.
[31]	Yang Y, Sun X, Xu J, et al. Circular bispecific aptamer-mediated artificial intercellular recognition for targeted T cell immunotherapy[J].ACS Nano,2020,14(8): 9562-9571. DOI:10.1021/acsnano. 9b09884. pmid:32584540
[32]	Peng JJ, Wang L, Li Z, et al. Metabolic challenges and interventions in CAR T cell therapy[J].Sci Immunol,2023,8(82): eabq3016. DOI:10.1126/sciimmunol.abq3016.
[33]	Liu CG, Wang Y, Liu P, et al. Aptamer-T cell targeted therapy for tumor treatment using sugar metabolism and click chemistry[J].ACS Chem Biol,2020,15(6): 1554-1565. DOI:10.1021/acschembio.0c00164.
[34]	Menon AP, Villanueva H, Meraviglia-Crivelli D, et al. CD3 aptamers promote expansion and persistence of tumor-reactive T cells for adoptive T cell therapy in cancer[J].Mol Ther Nucleic Acids,2024,35(2): 102198. DOI:10.1016/j.omtn.2024.102198.
[35]	Porreca I, Blassberg R, Harbottle J, et al. An aptamer-mediated base editing platform for simultaneous knockin and multiple gene knockout for allogeneic CAR-T cells generation[J].Mol Ther,2024,32(8): 2692-2710. DOI:10.1016/j.ymthe.2024.06.033.
[36]	Liu Y, Qian X, Ran C, et al. Aptamer-based targeted protein degradation[J].ACS Nano,2023,17(7): 6150-6164. DOI:10. 1021/acsnano.2c10379.
[37]	He S, Gao F, Ma J, et al. Aptamer-PROTAC conjugates (APCs) for tumor-specific targeting in breast cancer[J].Angew Chem Int Ed Engl,2021,60(43): 23299-23305. DOI:10.1002/anie.202107347.
[38]	Zhang L, Li L, Wang X, et al. Development of a novel PROTAC using the nucleic acid aptamer as a targeting ligand for tumor selective degradation of nucleolin[J].Mol Ther Nucleic Acids,2022,30: 66-79. DOI:10.1016/j.omtn.2022.09.008.
[39]	Wang Y, Yang G, Zhang X, et al. Antitumor effect of anti-c-Myc aptamer-based PROTAC for degradation of the c-Myc protein[J].Adv Sci (Weinh),2024,11(26): 2309639. DOI:10.1002/advs. 202309639.