Gold Nanobipyramids as Dual-Functional Substrates for in Situ “Turn On” Analyzing Intracellular Telomerase Activity Based on Target-Triggered Plasmon-Enhanced Fluorescence

Herein, we developed a novel plasmon-enhanced fluorescence (PEF)-based telomerase-responsive nanoprobe for in situ fluorescence "turn on" visualization of telomerase activity in live cells. The as-prepared nanoprobe was composed of a nicked molecular beacon (which contains Cy5.5-labeled hairpin-DNA sequences hybridized with telomerase primers)-functionalized gold nanobipyramids (Au NBPs). Au NBPs were selected as both fluorescence resonance energy-transfer and PEF dual-functional substrates, while DNA was selected to be the precise spacer to manage the interval between the Au NBPs and Cy5.5. On the basis of this target-triggered PEF probe, optimal fluorescence enhancement can be obtained with 49 DNA bases, which was higher than gold nanorods. The proposed method accomplishes sensitive telomerase activity detection down to 23 HeLa cells with a dynamic range of 40–1200 HeLa cells. On the basis of this, in situ fluorescence imaging of telomerase activity in live cells and real-time analysis of the variation in intracellular telomerase activity can be achieved. Moreover, cancer cells and normal cells can also be successfully discriminated even in their co-cultured mixtures, indicating promising potential in clinical diagnoses.