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原位自动DNA组装辅助鉴定双重治疗靶点用于乳腺癌联合治疗

Identification of dual therapeutic targets assisted by in situ automatous DNA assembly for combined therapy in breast cancer.

作者信息

Han Bing, Sha Lingjun, Yu Xiaomeng, Yang Mei, Cao Ya, Zhao Jing

机构信息

Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.

Minhang Branch, Fudan University Shanghai Cancer Center, Shanghai, 200240, PR China.

出版信息

Biosens Bioelectron. 2021 Mar 15;176:112913. doi: 10.1016/j.bios.2020.112913. Epub 2020 Dec 17.

Abstract

Breast cancer is the most common malignant disease among women worldwide. Nowadays, combined therapy against several therapeutic targets is becoming a promising treatment to enhance the survival rate of the patients with some lethal subtypes, and also proposes high demand on the discrimination of the co-existing targets in breast cancer. In this work, we designed in situ automatous DNA assembly reaction and applied it for the simultaneous identification of dual therapeutic targets using electrochemical techniques. Taking triple-negative breast cancer cell MDA-MB-231 as a model, chained strand displacement reactions were initiated after the capture probes recognized the surface biomarkers, epidermal growth factor receptor and intercellular adhesion molecule-1, respectively. Then, an increased electrochemical signaling was created to reveal the co-expression of the two targets using quantum dots as electrochemical labeling. Electrochemical results demonstrated high sensitivity and specificity of our method toward the identification of the coexisted therapeutic targets even in the serum samples, which also allowed to monitor the enhanced efficiency of combined therapy. Therefore, our method suggested a potential use in the accurate identification of therapeutic targets in breast cancer that might provide more information to facilitate the combined therapy in clinic.

摘要

乳腺癌是全球女性中最常见的恶性疾病。如今,针对多个治疗靶点的联合疗法正成为一种有前景的治疗方法,以提高某些致死性亚型患者的生存率,同时也对乳腺癌中共存靶点的鉴别提出了很高的要求。在这项工作中,我们设计了原位自动DNA组装反应,并将其应用于使用电化学技术同时鉴定双重治疗靶点。以三阴性乳腺癌细胞MDA-MB-231为模型,捕获探针分别识别表面生物标志物表皮生长因子受体和细胞间黏附分子-1后,引发链式链置换反应。然后,使用量子点作为电化学标记物,产生增强的电化学信号以揭示两个靶点的共表达。电化学结果表明,我们的方法对共存治疗靶点的鉴定具有高灵敏度和特异性,即使在血清样本中也是如此,这也能够监测联合治疗的增强效果。因此,我们的方法表明在准确鉴定乳腺癌治疗靶点方面具有潜在用途,这可能提供更多信息以促进临床联合治疗。

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