A signal-amplifiable biochip quantifies extracellular vesicle-associated RNAs for early cancer detection

作者：Jiaming Hu, Yan Sheng, Kwang Joo Kwak, Junfeng Shi, Bohao Yu, L. James Lee · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/s41467-017-01942-1 · 被引用次数：174 · 研究领域：Extracellular vesicles in disease、Advanced biosensing and bioanalysis techniques、MicroRNA in disease regulation

Detection of extracellular vesicle (EV)-associated RNAs with low expression levels in early-stage cancer remains a challenge and is highly valuable. Here, we report a nanoparticle-based biochip that could capture circulating EVs without isolation, brighten encapsulated RNAs, and amplify fluorescence signals in situ in a single step. We confine catalyzed hairpin DNA circuit (CHDC) in cationic lipid-polymer hybrid nanoparticles (LPHNs) that are tethered on a chip. LPHN features a core-shell-corona structure that facilitates the transfer and mixing of CHDC with EV-associated RNAs when forming the LPHN-EV nanocomplex. CHDC is triggered upon target RNA binding and quickly generate amplified signals. The signal amplification efficiency of LPHN-CHDC is demonstrated in artificial EVs, cancer cells, and cancer cell-derived EVs. We show that LPHN-CHDC biochip with signal amplification capability could selectively and sensitively identify low expression glypican-1 mRNA in serum EVs, distinguishing patients with early- and late-stage pancreatic cancer from healthy donors and patients with benign pancreatic disease.