Biobank, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.
Anal Chem. 2024 Mar 12;96(10):4154-4162. doi: 10.1021/acs.analchem.3c05085. Epub 2024 Mar 1.
Metastasis is the leading cause of death in patients with breast cancer. Detecting high-risk breast cancer, including micrometastasis, at an early stage is vital for customizing the right and efficient therapies. In this study, we propose an enzyme-free isothermal cascade amplification-based DNA logic circuit in situ biomineralization nanosensor, HDNAzyme@ZIF-8, for simultaneous imaging of multidimensional biomarkers in live cells. Taking miR-21 and Ki-67 mRNA as the dual detection targets achieved sensitive logic operations and molecular recognition through the cascade hybridization chain reaction and DNAzyme. The HDNAzyme@ZIF-8 nanosensor has the ability to accurately differentiate breast cancer cells and their subtypes by comparing their relative fluorescence intensities. Of note, our nanosensor can also achieve visualization within breast cancer organoids, faithfully recapitulating the functional characteristics of parental tumor. Overall, the combination of these techniques offers a universal strategy for detecting cancers with high sensitivity and holds vast potential in clinical cancer diagnosis.
转移是乳腺癌患者死亡的主要原因。早期发现包括微转移在内的高危乳腺癌对于定制正确有效的治疗方法至关重要。在这项研究中，我们提出了一种基于无酶等温级联扩增的 DNA 逻辑电路原位生物矿化纳米传感器 HDNAzyme@ZIF-8，用于在活细胞中同时对多维生物标志物进行成像。以 miR-21 和 Ki-67 mRNA 作为双检测靶点，通过级联杂交链式反应和 DNA 酶实现了敏感的逻辑运算和分子识别。HDNAzyme@ZIF-8 纳米传感器通过比较其相对荧光强度，能够准确地区分乳腺癌细胞及其亚型。值得注意的是，我们的纳米传感器还可以在乳腺癌类器官内实现可视化，忠实地再现亲本肿瘤的功能特征。总的来说，这些技术的结合为高灵敏度检测癌症提供了一种通用策略，在临床癌症诊断中具有广阔的应用前景。
