期刊
CHEMICAL SCIENCE
卷 8, 期 4, 页码 2832-2840出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6sc04633a
关键词
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资金
- National Natural Science Foundation of China [21305035]
- Hong Kong Scholars Program
- Fundamental Research Funds for the Central Universities
- Hunan Provincial Natural Science Foundation [14JJ3066]
- Research Grant Council of Hong Kong [HKBU201612, C2012-15G]
- Hong Kong Baptist University [FRG2/14-15/057]
Efficient strategies for the ultrasensitive imaging of gene expression in living cells are essential in chemistry and cell biology. Here, we report a novel and efficient enzyme-free dual signal amplification strategy for live cell mRNA imaging by using a smart nucleic acid hairpin-based nanosystem. This nanosystem consists of a ZnO nanoparticle core, an interlayer of polydopamine and an outer layer of four hairpin DNA (hpDNA) probes. Such a core-shell nanosystem facilitates the cellular uptake of molecular hairpin payloads, protects them from nuclease digestion, and delivers them into the cytoplasm by the acid-triggered dissolution of the ZnO core. In the presence of target mRNA, the released hpDNA probes self-assemble via HCR into wire-shaped active DNAzymes that catalyze the generation of a fluorescence signal. The target-initiated HCR events and DNAzyme cascades offer efficient dual amplification and enable the ultrasensitive detection of mRNA with a femtomolar detection limit. Live cell assays show an intense fluorescence response from a tumor-related biomarker survivin mRNA only in tumor cells untreated with a survivin expression repressor YM155, but not in normal cells. The developed nanosystem provides a potential platform for the amplified imaging of low-abundance disease-related biomarkers in live cells.
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