Catalytic Molecular Imaging of MicroRNA in Living Cells by DNA‐Programmed Nanoparticle Disassembly

He, Xuewen; Zeng, Tao; Li, Zhi; Wang, Ganglin; Ma, Nan

doi:10.1002/ange.201509726

Cited by 64 publications

(46 citation statements)

References 35 publications

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“…1–7 Extensive research efforts have been paid to explore sensitive technologies for the detection of miRNAs. 8–13 Furthermore, it is of great significance to measure a panel of miRNAs and thus give precise and accurate detection of cancers. 14,15 On the other hand, imaging of miRNAs in situ in living cells could recognize cancerous cells directly.…”

Section: Introductionmentioning

confidence: 99%

MnO₂ Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

Ericson

Yang

et al. 2017

ACS Appl. Mater. Interfaces

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Sensitive assay and imaging of multiple low-abundance microRNAs (miRNAs) in living cells remain a grand challenge. Herein, based on polyelectrolyte induced reduction, a facile approach has been proposed to synthesize novel MnO2 nanotubes. Owing to the remarkably strong fluorescence quenching ability, low cytotoxicity and excellent colloid stability, the as-prepared MnO2 nanotubes showed great potential for simultaneous detection and imaging of multiple miRNAs in vitro and in situ in living cells for the first time. Besides, MnO2 nanotubes can be reduced to Mn2+ by intracellular acid pH or glutathione, which may serve as activatable contrast reagent for MRI. Therefore, the MnO2 nanotubes based probes, termed “NanoSearchlight”, provide a promising, multimodal imaging tool for precise and accurate diagnosis and prognosis of cancers.

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Section: Introductionmentioning

confidence: 99%

MnO₂ Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

Ericson

Yang

et al. 2017

ACS Appl. Mater. Interfaces

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“…The intracellular target survivin mRNA then hybridized with one H1 in DNSL to trigger the cascade hybridization of H1 and H2 along the DNA nanowire due to their alternate arrangement in DNSL and programmed distance, which could instantly light up the whole DNSL with highly amplified signal gain (Scheme 1b). Compared with previously reported nonenzymatic catalytic amplification techniques 30,31 and successive DNA hybridization on nanoplatform, [27][28][29] 5 the DNSL contained numbers of H1 and H2 as successive reactants in a confined space, which not only accelerated the reaction with high efficiency, but also enhanced the detection sensitivity with high signal gain. The biocompatible DNSL as a delivery vehicle also facilitated the intracellular delivery without the usage of exotic transfection reagents.…”

mentioning

confidence: 99%

A Responsive “Nano String Light” for Highly Efficient mRNA Imaging in Living Cells via Accelerated DNA Cascade Reaction

et al. 2017

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Nonenzymatic DNA catalytic amplification strategies have greatly benefited bioanalysis. However, long period incubation is usually required due to its relatively low reaction rate and efficiency, which limits its in vivo application. Here we design a responsive DNA nano string light (DNSL) by interval hybridization of modified hairpin DNA probe pairs to a DNA nanowire generated by rolling circle amplification and realize accelerated DNA cascade reaction (DCR) for fast and highly efficient mRNA imaging in living cells. Target mRNA initiates interval hybridization of two paired hairpin probes sequentially along the DNA nanowire and results in instant lighting up of the whole DNA nanowire with high signal gain due to the fast opening of all the self-quenched hairpins. The reaction time is about 6.7 times shorter compared with a regular DNA cascade reaction due to the acceleration based on domino effect. The cell delivery is achieved by modifying one of the hairpin probes with folic acid, and this intracellular imaging strategy is verified using human HeLa cells and intracellular survivin mRNA with a series of suppressed expressions as model, which provides a useful platform for fast and highly efficient detection of low-abundance nucleic acids in living cells.

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“…21 In addition, complex steps for the preparation and functionalization of these nanomaterials are commonly required. 22,23 …”

mentioning

confidence: 99%

Fluorescence Resonance Energy Transfer-Based DNA Tetrahedron Nanotweezer for Highly Reliable Detection of Tumor-Related mRNA in Living Cells

et al. 2017

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Accurate detection and imaging of tumor-related mRNA in living cells hold great promise for early cancer detection. However, currently, most probes designed to image intracellular mRNA confront intrinsic interferences arising from complex biological matrices and resulting in inevitable false-positive signals. To circumvent this problem, an intracellular DNA nanoprobe, termed DNA tetrahedron nanotweezer (DTNT), was developed to reliably image tumor-related mRNA in living cells based on the FRET (fluorescence resonance energy transfer) “off” to “on” signal readout mode. DTNT was self-assembled from four single-stranded DNAs. In the absence of target mRNA, the respectively labeled donor and acceptor fluorophores are separated, thus inducing low FRET efficiency. However, in the presence of target mRNA, DTNT alters its structure from the open to closed state, thus bringing the dual fluorophores into close proximity for high FRET efficiency. The DTNT exhibited high cellular permeability, fast response and excellent biocompatibility. Moreover, intracellular imaging experiments showed that DTNT could effectively distinguish cancer cells from normal cells and, moreover, distinguish among changes of mRNA expression levels in living cells. The DTNT nanoprobe also exhibits minimal effect of probe concentration, distribution and laser power as other ratiometric probe. More importantly, as a result of the FRET “off” to “on” signal readout mode, the DTNT nanoprobe almost entirely avoids false-positive signals due to intrinsic interferences, such as nuclease digestion, protein binding and thermodynamic fluctuations in complex biological matrices. This design blueprint can be applied to the development of powerful DNA nanomachines for biomedical research and clinical early diagnosis.

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Catalytic Molecular Imaging of MicroRNA in Living Cells by DNA‐Programmed Nanoparticle Disassembly

Cited by 64 publications

References 35 publications

MnO₂ Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

MnO₂ Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

A Responsive “Nano String Light” for Highly Efficient mRNA Imaging in Living Cells via Accelerated DNA Cascade Reaction

Fluorescence Resonance Energy Transfer-Based DNA Tetrahedron Nanotweezer for Highly Reliable Detection of Tumor-Related mRNA in Living Cells

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Catalytic Molecular Imaging of MicroRNA in Living Cells by DNA‐Programmed Nanoparticle Disassembly

Cited by 64 publications

References 35 publications

MnO2 Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

MnO2 Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

A Responsive “Nano String Light” for Highly Efficient mRNA Imaging in Living Cells via Accelerated DNA Cascade Reaction

Fluorescence Resonance Energy Transfer-Based DNA Tetrahedron Nanotweezer for Highly Reliable Detection of Tumor-Related mRNA in Living Cells

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MnO₂ Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

MnO₂ Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells