Liu Mei, Zhang Biao, Li Zhiyang, Wang Zhifei, Li Song, Liu Hongna, Deng Yan, He Nongyue
State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education (Southeast University), School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China.
Nanoscale. 2020 Oct 14;12(38):19689-19701. doi: 10.1039/d0nr03324c. Epub 2020 Sep 23.
Precise discrimination of breast cancer remains a challenge in clinical medicine, which depends on the development of novel specific molecular probes. However, the current technologies and antibodies cannot achieve precise discrimination of breast cancer subtypes very well. To address this problem, a novel truncated DNA aptamer MF3Ec was developed in this work. Aptamer MF3Ec exhibited high specificity and binding affinity against MCF-7 breast cancer cells with a K value of 18.95 ± 2.9 nM which is four times lower than that of the original aptamer, and could work at 4 °C, 25 °C and 37 °C with no obvious differences. Besides, aptamer MF3Ec displayed better stability in serum samples with a long existence time of about 12 h. Moreover, fluorescence imaging experiments indicated that aptamer MF3Ec was able to distinguish MCF-7 breast cancer cells from SK-BR-3, MDA-MB-231 and MCF-10A breast cancer cell subtypes, and differentiate the tumor-bearing mice and xenografted tissue sections of MCF-7 breast cancer cells from those of MDA-MB-231 and SK-BR-3 breast cancer cells in vivo and in vitro, respectively. Finally, clinical experiments indicated that aptamer MF3Ec could distinguish Luminal A breast cancer subtype from Luminal B (HER2+), HER2-enriched, and triple-negative breast cancer subtypes, para-carcinoma tissues and normal breast tissues. Collectively, all these results suggest that aptamer MF3Ec is a promising probe for precise discrimination and targeted therapy of Luminal A breast cancer molecular subtype.
在临床医学中，对乳腺癌进行精确鉴别仍然是一项挑战，这依赖于新型特异性分子探针的开发。然而，当前的技术和抗体无法很好地实现对乳腺癌亚型的精确鉴别。为了解决这个问题，本研究开发了一种新型截短的DNA适配体MF3Ec。适配体MF3Ec对MCF-7乳腺癌细胞表现出高特异性和结合亲和力，K值为18.95±2.9 nM，比原始适配体低四倍，并且可以在4℃、25℃和37℃下工作，没有明显差异。此外，适配体MF3Ec在血清样本中显示出更好的稳定性，存在时间约为12小时。此外，荧光成像实验表明，适配体MF3Ec能够区分MCF-7乳腺癌细胞与SK-BR-3、MDA-MB-231和MCF-10A乳腺癌细胞亚型，并分别在体内和体外区分MCF-7乳腺癌细胞的荷瘤小鼠和异种移植组织切片与MDA-MB-231和SK-BR-3乳腺癌细胞的荷瘤小鼠和异种移植组织切片。最后，临床实验表明，适配体MF3Ec可以区分Luminal A乳腺癌亚型与Luminal B（HER2+）、HER2富集型和三阴性乳腺癌亚型、癌旁组织和正常乳腺组织。总的来说，所有这些结果表明，适配体MF3Ec是一种有前途的用于精确鉴别和靶向治疗Luminal A乳腺癌分子亚型的探针。
