DNA Nanowire Guided-Catalyzed Hairpin Assembly Nanoprobe for <i>In Situ</i> Profiling of Circulating Extracellular Vesicle-Associated MicroRNAs
Ye Zhang, Yuan Wu, Shihua Luo, Chao Yang, Guangzhi Zhong, Guoni Huang, Xiaohe Zhang, Bo Li, Chunchen Liu, Ling Li, Xiaohui Yan, Lei Zheng, Bo Situ
Abstract
Extracellular vesicle-associated miRNAs (EV-miRNAs) are emerging as a new type of noninvasive biomarker for disease diagnosis. Their relatively low abundance, however, makes accurate detection challenging. Here, we designed a DNA nanowire guided-catalyzed hairpin assembly (NgCHA) nanoprobe for profiling EV-miRNAs. NgCHA showed high penetrability to EVs, which allowed rapid delivery of the probes into EVs. In the presence of targeted miRNAs within EVs, a fluorescent signal could be generated and amplified by confining the catalytic hairpin assembly system within the nanowires, thus greatly enhancing the analytical sensitivity. We showed that EV-miRNAs from various cell lines could be accurately quantified by NgCHA in situ. By using a four-EV-miRNA panel, this platform can identify patients with breast cancer at an early stage with 95.2% sensitivity and 86.7% specificity. Its applications for risk assessment as well as cancer type prediction were also successfully demonstrated. This platform is sensitive, low-cost, and simple compared with current methods. It may thus serve as a promising tool for the noninvasive diagnosis and monitoring of cancers and other diseases through EV-miRNA profiling.