基于核酸适配体的肺癌诊断和治疗研究进展

doi:10.3969/j.issn.1004-583X.2025.08.013

摘要/Abstract

摘要：

肺癌是全球发病率和死亡率最高的恶性肿瘤之一,其早期诊断困难、肿瘤异质性和治疗耐药性等问题严重制约其临床疗效的提升。传统诊疗手段在精准性与个体化方面存在局限,因此有必要开发新型分子工具以突破技术瓶颈。核酸适配体是通过体外筛选获得的单链DNA或RNA片段,凭借其高亲和力、低免疫原性及灵活的可设计性,可靶向肿瘤标志物实现早期诊断、无创液体活检及精准药物递送。此外,核酸适配体能与现代先进诊疗技术相融合,在分子成像、靶向治疗和动态监测等领域具有广阔的应用前景。本文综述了核酸适配体在肺癌诊疗中的前沿进展,探讨其技术优势、应用场景及转化挑战,为肺癌的精准诊疗体系提供理论支撑与创新方向。

关键词: 肺肿瘤, 核酸适配体, 精准诊疗, 靶向治疗, 液体活检

中图分类号:

R734.2

陈文江, 舒展, 周来显. 基于核酸适配体的肺癌诊断和治疗研究进展[J]. 临床荟萃, 2025, 40(8): 742-747.

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链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2025.08.013

https://www.lchc.cn/CN/Y2025/V40/I8/742

参考文献 60

[1]	Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: Current status and future trends[J]. Nat Rev Clin Oncol, 2023, 20(9): 624-639. doi: 10.1038/s41571-023-00798-3 pmid: 37479810
[2]	Li Y, Yan B, He S. Advances and challenges in the treatment of lung cancer[J]. Biomed Pharmacother, 2023, 169: 115891.
[3]	Adams SJ, Stone E, Baldwin DR, et al. Lung cancer screening[J]. Lancet, 2023, 401(10374): 390-408. doi: 10.1016/S0140-6736(22)01694-4 pmid: 36563698
[4]	Jha SK, De Rubis G, Devkota SR, et al. Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions[J]. Ageing Res Rev, 2024, 97: 102315.
[5]	Hu X, Zhang D, Zeng Z, et al. Aptamer-based probes for cancer diagnostics and treatment[J]. Life (Basel), 2022, 12(11):1937.
[6]	Nimjee SM, White RR, Becker RC, et al. Aptamers as therapeutics[J]. Annu Rev Pharmacol Toxicol, 2017, 57: 61-79. doi: 10.1146/annurev-pharmtox-010716-104558 pmid: 28061688
[7]	Ding Z, Wang N, Ji N, et al. Proteomics technologies for cancer liquid biopsies[J]. Mol Cancer, 2022, 21(1): 53. doi: 10.1186/s12943-022-01526-8 pmid: 35168611
[8]	Kumar Kulabhusan P, Hussain B, Yüce M. Current perspectives on aptamers as diagnostic tools and therapeutic agents[J]. Pharmaceutics, 2020, 12(7):646.
[9]	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
[10]	Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands[J]. Nature, 1990, 346(6287): 818-822.
[11]	Jayasena SD. Aptamers: An emerging class of molecules that rival antibodies in diagnostics[J]. Clin Chem, 1999, 45(9): 1628-1650. pmid: 10471678
[12]	Zhao H, Xiang X, Chen M, et al. Aptamer-based fluorometric ochratoxin:A assay based on photoinduced electron transfer[J]. Toxins, 2019, 11(2):56.
[13]	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 pmid: 37468977
[14]	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.
[15]	Chinchilla-Cárdenas DJ, Cruz-Méndez JS, Petano-Duque JM, et al. Current developments of SELEX technologies and prospects in the aptamer selection with clinical applications[J]. J Genet Eng Bio technol, 2024, 22(3): 100400.
[16]	Hu Y, Jiang G, Wen Y, et al. Selection of aptamers targeting small molecules by capillary electrophoresis: Advances, challenges, and prospects[J]. Biotechnol Adv, 2025, 78: 108491.
[17]	Nooreldeen R, Bach H. Current and future development in lung cancer diagnosis[J]. Int J Mol Sc, 2021, 22(16):8661.
[18]	Wu L, Wang Y, Xu X, et al. Aptamer-based detection of circulating targets for precision medicine[J]. Chem Rev, 2021, 121(19): 12035-12105. doi: 10.1021/acs.chemrev.0c01140 pmid: 33667075
[19]	Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer[J]. Semin Cancer Biol, 2020, 61: 167-179. doi: S1044-579X(19)30302-5 pmid: 31562956
[20]	Reita D, Pabst L, Pencreach E, et al. Molecular mechanism of EGFR-TKI resistance in egfr-mutated non-small cell lung cancer: Application to biological diagnostic and monitoring[J]. Cancers, 2021, 13(19):4926.
[21]	Thomas BJ, Guldenpfennig C, Guan Y, et al. Targeting lung cancer with clinically relevant EGFR mutations using anti-EGFR RNA aptamer[J]. Mol Ther Nucleic Acids, 2023, 34: 102046.
[22]	钱哲, 胡瑛, 林根. 晚期肺癌PD1/PD-L1单抗免疫治疗现状与思考[J]. 中国临床新医学, 2024, 17(12): 1325-1330.
[23]	郭义城, 武海滨, 杨颖, 等. 全新靶向小分子核酸适配体特异性检测肺癌患者血清标志物的应用研究[J]. 临床医学研究与实践, 2020, 5(1): 1-4+9.
[24]	Zhao Y, He L, Huang B, et al. Identification of a novel DNA aptamer that selectively targets lung cancer serum[J]. RSC Adv, 2021, 11(53): 33759-33769. doi: 10.1039/d1ra06233f pmid: 35497520
[25]	Quansah M, Fetter L, Fineran A, et al. Rapid and quantitative detection of lung cancer biomarker ENOX2:Using a novel aptamer in an electrochemical DNA-Based (E-DNA) biosensor[J]. Biosensors, 2023, 13(7):675.
[26]	Chen X, Li Y, Su J, et al. Progression in near-infrared fluorescence imaging technology for lung cancer management[J]. Biosensors, 2024, 14(10):501.
[27]	Xiong H, Yan J, Cai S, et al. Cancer protein biomarker discovery based on nucleic acid aptamers[J]. Int J Biol Macromol, 2019, 132: 190-202. doi: S0141-8130(18)37343-4 pmid: 30926499
[28]	Ren X, Li J, Wu X, et al. A highly specific aptamer probe targeting PD-L1 in tumor tissue sections: Mutation favors specificity[J]. Anal Chim Acta, 2021, 1185: 339066.
[29]	Liu X, Chen Y, Zhang F, et al. Preclinical evaluation of ga-labeled SL1 aptamer for c-met targeted pet imaging[J]. Mol Pharm, 2025, 22(3):1615-1623.
[30]	Bouvier-Müller A, Ducongé F. Application of aptamers for in vivo molecular imaging and theranostics[J]. Adv Drug Deliv Rev, 2018, 134: 94-106.
[31]	Li W, Liu JB, Hou LK, et al. Liquid biopsy in lung cancer: Significance in diagnostics, prediction, and treatment monitoring[J]. Mol Cancer, 2022, 21(1): 25. doi: 10.1186/s12943-022-01505-z pmid: 35057806
[32]	Casagrande GMS, Silva MO, Reis RM, et al. Liquid biopsy for lung cancer: Up-to-date and perspectives for screening programs[J]. Int J Mol Sci, 2023, 24(3).
[33]	Ren F, Fei Q, Qiu K, et al. Liquid biopsy techniques and lung cancer: Diagnosis, monitoring and evaluation[J]. J Exp Clin Cancer Res, 2024, 43(1): 96. doi: 10.1186/s13046-024-03026-7 pmid: 38561776
[34]	Jiménez W. Liquid biopsy: A challenge for clinical laboratories[J]. Adv Lab Med, 2020, 1(3): 20200055.
[35]	Hong B, Zu Y. Detecting circulating tumor cells: Current challenges and new trends[J]. Theranostics, 2013, 3(6): 377-394. doi: 10.7150/thno.5195 pmid: 23781285
[36]	Liu Y, Zhang B, Wu X, et al. A facile liquid biopsy assay for highly efficient CTCs capture and reagent-less monitoring of immune checkpoint PD-L1 expression on CTCs with non-small cell lung cancer patients[J]. Biosens Bioelectron, 2025, 275: 117236.
[37]	Zhou Y, Zhang Y, Gong H, et al. The role of exosomes and their applications in cancer[J]. Int J Mol Sci, 2021, 22(22):12204.
[38]	Zhao L, Wang H, Fu J, et al. Microfluidic-based exosome isolation and highly sensitive aptamer exosome membrane protein detection for lung cancer diagnosis[J]. Biosens Bioelectron, 2022, 214: 114487.
[39]	Zhu N, Li G, Zhou J, et al. A light-up fluorescence resonance energy transfer magnetic aptamer-sensor for ultra-sensitive lung cancer exosome detection[J]. J Mater Chem B, 2021, 9(10): 2483-2493. doi: 10.1039/d1tb00046b pmid: 33656037
[40]	Yu Q, Zhao Q, Wang S, et al. Development of a lateral flow aptamer assay strip for facile identification of theranostic exosomes isolated from human lung carcinoma cells[J]. Anal Biochem, 2020, 594: 113591.
[41]	Hashemian Z, Khayamian T, Saraji M, et al. Aptasensor based on fluorescence resonance energy transfer for the analysis of adenosine in urine samples of lung cancer patients[J]. Biosens Bioelectron, 2016, 79: 334-340. doi: 10.1016/j.bios.2015.12.028 pmid: 26722763
[42]	Rotoli D, Santana-Viera L, Ibba ML, et al. Advances in oligonucleotide aptamers for NSCLC targeting[J]. Int J Mol Sci, 2020, 21(17):6075.
[43]	Zhu L, Zhao J, Guo Z, et al. Applications of aptamer-bound nanomaterials in cancer therapy[J]. Biosensors, 2021, 11(9):344.
[44]	Yin X, He Z, Ge W, et al. Application of aptamer functionalized nanomaterials in targeting therapeutics of typical tumors[J]. Front Bioeng Biotechnol, 2023, 11: 1092901.
[45]	Xia B, Shaheen N, Chen H, et al. RNA aptamer-mediated RNA nanotechnology for potential treatment of cardiopulmonary diseases[J]. Pharmacol Res, 2025, 213: 107659.
[46]	Guo L, Chen H, He N, et al. Effects of surface modifications on the physicochemical properties of iron oxide nanoparticles and their performance as anticancer drug carriers[J]. Chin Chem Lett, 2018, 29(12): 1829-1833.
[47]	Zhao C, Song X, Jin W, et al. Image-guided cancer therapy using aptamer-functionalized cross-linked magnetic-responsive Fe₃O₄@carbon nanoparticles[J]. Anal Chim Acta, 2019, 1056: 108-116.
[48]	Zhang Y, Wang Q, Chen G, et al. DNA-functionalized metal-organic framework: Cell imaging, targeting drug delivery and photodynamic therapy[J]. Inorg Chem, 2019, 58(10): 6593-6596. doi: 10.1021/acs.inorgchem.9b00734 pmid: 31074268
[49]	Saravanakumar K, Sathiyaseelan A, Mariadoss A VA, et al. Dual stimuli-responsive release of aptamer AS1411 decorated erlotinib loaded chitosan nanoparticles for non-small-cell lung carcinoma therapy[J]. Carbohydr Polym, 2020, 245: 116407.
[50]	García Melián MF, Moreno M, Cerecetto H, et al. Aptamer-based immunotheranostic strategies[J]. Cancer Biother Radiopharm, 2023, 38(4): 246-255.
[51]	Lai WY, Huang BT, Wang JW, et al. A novel PD-L1-targeting antagonistic DNA aptamer with antitumor effects[J]. Mol Ther Nucleic Acids, 2016, 5(12): e397.
[52]	Cheng W, Kang K, Zhao A, et al. Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer[J]. J Hematol Oncol, 2024, 17(1): 54.
[53]	Soldevilla MM, Villanueva H, Meraviglia-Crivelli D, et al. ICOS costimulation at the tumor site in combination with CTLA-4 blockade therapy elicits strong tumor immunity[J]. Mol Ther, 2019, 27(11): 1878-1891. doi: S1525-0016(19)30326-0 pmid: 31405808
[54]	Tsai YT, Liang CH, Yu JH, et al. A DNA aptamer targeting galectin-1 as a novel immunotherapeutic strategy for lung cancer[J]. Mol Ther Nucleic Acids, 2019, 18: 991-998.
[55]	Reck M, Remon J, Hellmann MD. First-line immunotherapy for non-small-cell lung cancer[J]. J Clin Oncol, 2022, 40(6): 586-597. doi: 10.1200/JCO.21.01497 pmid: 34985920
[56]	Dessai A, Nayak UY, Nayak Y. Precision nanomedicine to treat non-small cell lung cancer[J]. Life Sci, 2024, 346: 122614.
[57]	Yang H, Liu Y, Chen L, et al. MiRNA-Based therapies for lung cancer: Opportunities and challenges?[J]. Biomolecules, 2023, 13(6):877.
[58]	Yang Y, Han Y, Sun Q, et al. Au-siRNA@aptamer nanocages as a high-efficiency drug and gene delivery system for targeted lung cancer therapy[J]. J Nanobiotechnology, 2021, 19(1): 54.
[59]	Li Z, Yang L, Wang H, et al. Non-small-cell lung cancer regression by siRNA delivered through exosomes that display EGFR RNA aptamer[J]. Nucleic Acid Ther, 2021, 31(5): 364-374. doi: 10.1089/nat.2021.0002 pmid: 33999716
[60]	Wei Y, Long S, Zhao M, et al. Regulation of cellular signaling with an aptamer inhibitor to impede cancer metastasis[J]. J Am Chem Soc, 2024, 146(1): 319-329. doi: 10.1021/jacs.3c09091 pmid: 38129955

基于核酸适配体的肺癌诊断和治疗研究进展

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