Double-stem Hairpin Probe and Ultrasensitive Colorimetric Detection of Cancer-related Nucleic Acids

Xu, Jianguo; Li, Hongling; Wu, Zai‐Sheng; Qian, Jun; Xue, Chang; Lee, Jia

doi:10.7150/thno.13533

Cited by 34 publications

(12 citation statements)

References 49 publications

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“…To efficiently quench the fluorescence before operation and sufficiently separate F from Q after the cleavage, a double-stem hairpin structure was adopted, in which the total number of base pairs is 18 (see more details on the base sequences of the components in Scheme S1). In the absence of target miRNA, TDHS–LSDz is inactivated by the locking strand and the double-stem hairpin structure can tightly lock the TDHS probe, substantially inhibiting the background fluorescence. When TDHS–LSDz enters live cells and encounters target miRNA, the locking strand is peeled off by target hybridization, releasing the locked arm and activating the DNAzyme.…”

Section: Results and Discussionmentioning

confidence: 99%

Stimuli-Responsive Autonomous-Motion Molecular Machine for Sensitive Simultaneous Fluorescence Imaging of Intracellular MicroRNAs

et al. 2021

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DNAzymes with enzymatic activity identified from random DNA pools by in vitro selection have recently attracted considerable attention. In this work, a DNAzyme-based autonomous-motion (AM) molecular machine is demonstrated for sensitive simultaneous imaging of different intracellular microRNAs (miRNAs). The AM molecular machine consists of two basic elements, one of which is a target-analogue-embedded double-stem hairpin substrate (TDHS) and the other is a locking-strand-silenced DNAzyme (LSDz). LSDz can be activated by target miRNA and catalytically cleave TDHS, generating Clv-TDHS and releasing free target analogue capable of triggering the next round of cleavage reaction. As such, the molecular machine can exert sustainable autonomous operation, producing an enhanced signal. Because the active target analogue comes from the machine itself and offers cyclical stimulation in a feedback manner, this target-induced autonomous cleavage circuit is termed a self-feedback circuit (SFC). The SFC-based molecular machine can be used to quantify miRNA-21 down to 10 pM without interference from nontarget miRNAs, indicating a substantial improvement in assay performance compared with its counterpart system without an SFC effect. Moreover, due to the enzyme-free process, the AM molecular machine is suitable for miRNA imaging in living cells, and the quantitative results are consistent with the gold standard PCR assay. More interestingly, the AM molecular machine can be used for the simultaneous fluorescence imaging of several intracellular miRNAs, enabling the accurate discrimination of cancerous cells (e.g., HeLa and MCF-7) from healthy cells. The SFC-based autonomous-motion machine is expected to be a promising tool for the research of molecular biology and early diagnosis of human diseases.

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Section: Results and Discussionmentioning

confidence: 99%

Stimuli-Responsive Autonomous-Motion Molecular Machine for Sensitive Simultaneous Fluorescence Imaging of Intracellular MicroRNAs

et al. 2021

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“…Jia and co‐workers designed a double‐stem hairpin probe based on a colorimetric detection system. When triggered by cancer‐related DNA, G‐quadruplex DNAzyme recovered and performed a colorimetric signal with 1 × 10 −15 m LOD . The DNAzyme was also divided into two inactive parts and assembled to form a complete DNAzyme with catalytic activity when triggered by the target substance.…”

Section: Dna Nanomaterialsmentioning

confidence: 99%

Micro/Nano Technology for Next‐Generation Diagnostics

Gao

Tang

et al. 2019

Small Methods

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There has been a constant and urgent need to upgrade the current diagnostic technologies to the next generation by utilizing innovative advanced technologies in order to meet new challenges. Micro/nano technology, a series of methods for design and manipulation materials at the micrometer and nanometer scales, which perfectly covers the key building blocks of life including cells, organelles, proteins, nucleic acids, and other components, has unique advantages over current diagnostic methods. For the applications of micro–nano technology in next‐generation diagnostics, three categories, including microchip‐based devices, DNA nanomachines, and DNA nanomaterials, are extensively reviewed. Specifically, for the microchip‐based devices, terahertz technology and surface acoustic wave technology show their ultrasensitivity of label‐free, amplification‐free diagnosis. For the DNA nanomachines, DNA tweezers, DNA robots, and DNA walkers exhibit a great potential for diagnosis with the arbitrary structures and controllable motion behaviors. For the DNA nanomaterials, DNA aptamers, DNAzymes, and hybrid DNA nanomaterials provide sensitive biorecognition elements and versatile signal transductions, which are demonstrated as promising material candidates for the next‐generation diagnostics. Through this review, it is envisioned that micro/nano technologies will play an important role in the next‐generation diagnostics.

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“…Theranostic strategy is useful for real-time monitoring of in vivo delivery and therapeutic response of the drug candidate. Despite the significant attempts made in nanomedicine to combine therapeutic and diagnostic properties in a single formulation, there are no concerted reports on small molecule theranostics, except for few prodrugs 24 - 32 .…”

Section: Introductionmentioning

confidence: 99%

Recognition of G-quadruplex topology through hybrid binding with implications in cancer theranostics

et al. 2020

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The selective recognition and imaging of oncogene specific G-quadruplex (GQ) structures holds great promise in the development of diagnostic therapy (theranostics) for cancer and has been challenging due to their structural dynamics and diversity. We report selective recognition of GQ by a small molecule through unique hybrid loop stacking and groove binding mode with turn on far-red fluorescence response and anticancer activity demonstrating the potential implications for GQ-targeted cancer theranostics. Methods: Biophysical investigation reveal the turn on far-red emission property of TGP18 for selective recognition of GQ. In cellulo studies including DNA damage and oxidative stress evaluation guided us to perform in vitro (3D spheroid) and in vivo (xenograft mice model) anti-cancer activity, and tumor tissue imaging to assess the theranostic potential of TGP18. Results: Neocuproine-based far-red turn on fluorescence probe TGP18 shows GQ-to-duplex selectivity and specifically recognizes BCL-2 GQ with high affinity through a unique hybrid binding mode involving loop-stacking and groove interactions. Our study reveals that the selective recognition originating from the distinct loop structure of GQ that alters the overall probe interaction and binding affinity. TGP18 binding to anti-apoptotic BCL-2 GQ ablates the pro-survival function and elicit anti-cancer activity by inducing apoptosis in cancer cells. We deciphered that inhibition of BCL-2 transcription synergized with signaling cascade of nucleolar stress, DNA damage and oxidative stress in triggering apoptosis signaling pathway. Conclusion: Intervention of GQ mediated lethality by TGP18 has translated into anti-cancer activity in both in vitro 3D spheroid culture and in vivo xenograft models of lung and breast cancer with superior efficacy for the former. In vivo therapeutic efficacy supplemented with tumor 3D spheroid and tissue imaging potential define the role of TGP18 in GQ-targeted cancer theranostics.

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Double-stem Hairpin Probe and Ultrasensitive Colorimetric Detection of Cancer-related Nucleic Acids

Cited by 34 publications

References 49 publications

Stimuli-Responsive Autonomous-Motion Molecular Machine for Sensitive Simultaneous Fluorescence Imaging of Intracellular MicroRNAs

Stimuli-Responsive Autonomous-Motion Molecular Machine for Sensitive Simultaneous Fluorescence Imaging of Intracellular MicroRNAs

Micro/Nano Technology for Next‐Generation Diagnostics

Recognition of G-quadruplex topology through hybrid binding with implications in cancer theranostics

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