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基于核酸适体L4的转移性结直肠癌靶向成像研究

李欣岩1,孙诗涵1,苗滋伟2,耿文倩1,蒋  彬1,孙志英1,李婉明1
  

  1. 1. 中国医科大学生命科学学院,医学细胞生物学教育部重点实验室暨卫生部细胞生物学重点实验室,细胞生物学教研室 2. 中国医科大学生命科学学院发育细胞生物学教研室
  • 收稿日期:2026-02-13 修回日期:2026-05-07 网络首发:2026-05-09 发布日期:2026-05-09
  • 通讯作者: 李婉明 E-mail:wmli@cmu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号:82373445)和辽宁省科学技术计划项目(批准号:2023JH2/20200155)资助

Research on Targeted Imaging of Metastatic Colorectal Cancer Based on Aptamer L4

LI Xinyan1, SUN Shihan1, MIAO Ziwei2, GENG Wenqian1, JIANG Bin1, SUN Zhiying1, LI Wanming1*   

  1. 1. School of Life Sciences, China Medical University, Key Laboratory of Cell Biology of Ministry of Education and Key Laboratory of Cell Biology of Ministry of Health, Cell Biology Teaching and Research Office 2. Department of Developmental Cell Biology, School of Life Sciences, China Medical University
  • Received:2026-02-13 Revised:2026-05-07 Online First:2026-05-09 Published:2026-05-09
  • Contact: Wan-Ming LI E-mail:wmli@cmu.edu.cn
  • Supported by:
    Supported by the National Natural Science Foundation of China (No.82373445) and the Liaoning Provincial Science and Technology Plan(No.2023JH2/20200155)

摘要: 摘要 目的 探讨核酸适体L4的靶向结合特性,并探讨其作为分子探针对临床结直肠癌患者组织的靶向成像,望为转移性结直肠癌的靶向诊断提供潜在的分子工具. 方法 采用流式细胞术分析核酸适体L4的结合特异性、亲和性、温度稳定性和细胞选择性;通过酶处理实验探讨核酸适体L4结合靶分子的性质;基于生物素-链霉亲和素的结合原理,将核酸适体L4与量子点偶联形成L4-QD探针,对临床结直肠癌患者组织进行靶向成像,并分析组织靶向性及与患者病理特征的相关性. 结果 核酸适体L4高特异性和高亲和力地结合靶细胞HCT116,Kd值为10.4 ± 1.7 nM,且具有良好的温度稳定性.临床组织成像显示,L4-QD探针能够对结直肠癌组织实现靶向成像,且荧光强度与患者AJCC临床分期和生存预后不良呈显著正相关. 结论 核酸适体L4对转移性结直肠癌细胞具有高特异性和高亲和力,与量子点偶联可实现结直肠癌组织的靶向成像,有望成为评估结直肠癌进展程度的潜在分子探针及转移性结直肠癌靶向诊断的新型工具.

关键词: 转移性结直肠癌, 核酸适体, 靶向成像, 量子点

Abstract: Abstract Objective To explore the targeting binding characteristics of aptamer L4 and its application as a molecular probe for targeted imaging of colorectal cancer tissues in clinical patients, with the aim of providing a potential molecular tool for targeted diagnosis of metastatic colorectal cancer. Methods Flow cytometry was used to detect the binding specificity, affinity, thermal stability and cell selectivity of aptamer L4. Enzyme treatment experiments were conducted to clarify the nature of the target molecule bound by aptamer L4. Based on the principle of biotin-streptavidin binding, aptamer L4 was conjugated with quantum dots to form L4-QD probes, and their targeted imaging of colorectal cancer tissues in clinical patients was observed. The targeting specificity of the tissues and its correlation with the pathological characteristics of the patients were analyzed. Results Aptamer L4 specifically and strongly binds to HCT116 cells with a Kd value of 10.4±1.7 nM and shows good thermal stability. Aptamer L4 has binding specificity for tumor cells with metastatic potential, suggesting that its target molecule is a cell surface membrane protein. Clinical tissue imaging shows that L4-QD probes can achieve targeted imaging of colorectal cancer tissues, and the fluorescence intensity is significantly positively correlated with the AJCC clinical stage and poor survival prognosis of the patients. Conclusion Aptamer L4 has high specificity and affinity for metastatic colorectal cancer cells. Conjugation with quantum dots enables targeted imaging of colorectal cancer tissues and is expected to become a potential molecular probe for assessing the progression of colorectal cancer and a new tool for targeted diagnosis of metastatic colorectal cancer.

Key words: Metastatic colorectal cancer, Aptamer, Targeted imaging, Quantum dots

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