Multivalent Self-Assembled DNA Polymer for Tumor-Targeted Delivery and Live Cell Imaging of Telomerase Activity

Zhu, Xiaoyu; Ye, Hongyan; Liu, Jinwen; Yu, Ru‐Qin; Jiang, Jian‐Hui

doi:10.1021/acs.analchem.8b04631

Cited by 37 publications

(25 citation statements)

References 29 publications

(49 reference statements)

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“…A limit of detection of 0.05 U L −1 and 0.01 U mL −1 was obtained for TE and APE1, respectively (Figure S4). These detection sensitivities were comparable to previously reported probes for the detection of TE or APE1 individually in cancer cells, [8a–c, 9] guaranteeing the application of TP–AP for the imaging of the correlated activity of the two enzymes. In addition, TP–AP displayed high specificity toward TE and APE1 over other enzymes (Figure S5).…”

Section: Figuresupporting

confidence: 84%

A Cooperatively Activatable, DNA‐based Fluorescent Reporter for Imaging of Correlated Enzymatic Activities

et al. 2021

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The dynamic variation of the expression profile and spatial landscape of multiple enzymes are crucial factors influencing tumor progression and drug treatment. However, the comprehensive analysis of these events has been hampered by the limitations of existing imaging technologies. Here we report a cooperatively activatable, DNA‐based fluorescent reporter programmed to detect the correlated activity of dual enzymes, telomerase (TE) and apurinic/apyrimidinic endonuclease 1 (APE1), both in vitro and in vivo. The conformational change of the DNA probe can be orthogonally triggered through TE‐induced DNA elongation and APE1‐mediated specific cleavage, producing a fluorescent signal for imaging the activity of the two enzymes in an AND‐gated manner. Furthermore, we demonstrate the capability of the system for specific tumor imaging through “dual lock‐and‐key” strategy, and visualizing the correlated enzymatic activities during drug treatment of cancer.

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Section: Figuresupporting

confidence: 84%

A Cooperatively Activatable, DNA‐based Fluorescent Reporter for Imaging of Correlated Enzymatic Activities

et al. 2021

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“…Furthermore, the FRET nanoflares cannot specifically target toward cancer cells. As an alternative, DNA nanostructures, as emerging and powerful tools, have been extensively employed in biosensing, imaging, and therapy. − They possesses potential advantages, such as low cost, ease of assembly, biocompatibility, stability, and high loading capacity. − …”

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confidence: 99%

Orderly Assembled, Self-Powered FRET Flares for MicroRNA Imaging in Live Cells

Wang

Yang

et al. 2021

Anal. Chem.

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Signal amplification provides unparalleled opportunities for visualizing low-abundance targets in living cells. However, self-powered signal amplification has not been achieved because of the lack of “fuel” in living cells. Thus, the aim of this work was to develop an integrated amplification platform for the detection of intracellular miRNA by itself. This system, termed self-powered FRET flares (SPF), was first established by self-assembly to form a DNA nanostructure, and then the FRET flares and fuel DNA as the driving force were precisely and orderly loaded on it, which was able to power target recycle and realize signal amplification without any auxiliary additives under the trigger of intracellular miRNA-21. In addition, it employed AS1411 aptamer to target specific cancer cells and facilitated cell internalization of assembly DNA nanostructures. As a proof of concept, we demonstrated that SPF enabled rapid response to miRNA-21 and improvement of the detection sensitivity compared to previously proposed FRET flares without amplification. This strategy is promising for advancing integrated and self-powered nanomachines to execute diverse tasks, facilitating their biological and medical application.

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“…The rapid growth in DNA nanotechnology provides a number of biocompatible strategies for construction and delivery of these intracellular probes . DNA nanostructures not only can be facilely assembled and modified with functional units under mild conditions − but also provide efficient carriers for noninvasive delivery. , For example, when DNA nanostructures conjugated with multiple ligands by self-assembly, binding affinity and cellular internalization have been improved without the loss of selectivity. , It is important to note that when DNA nanostructures are modified with different functional groups, the endocytosis pathways and distribution in cells are usually different …”

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confidence: 99%

“…10,11 For example, when DNA nanostructures conjugated with multiple ligands by self-assembly, binding affinity and cellular internalization have been improved without the loss of selectivity. 12,13 It is important to note that when DNA nanostructures are modified with different functional groups, the endocytosis pathways and distribution in cells are usually different. 14 To construct sensing probes with organelle-targeting abilities, a general method is to modify nanostructures with specific molecules.…”

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confidence: 99%

Ratiometric Fluorescent DNA Nanostructure for Mitochondrial ATP Imaging in Living Cells Based on Hybridization Chain Reaction

et al. 2021

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For intracellular molecular detection, the appropriate probes should include the abilities to enter target cells noninvasively, target specific sites, and then respond to the analytes reliably. Herein, a ratiometric fluorescent DNA nanostructure (RFDN) was designed for mitochondrial adenosine triphosphate (ATP) imaging in living cells. The DNA nanostructure was constructed by continuous hybridization of two hairpin DNA strands (HS1-Cy3 and HS2-Cy5) under the initiation of the trigger. HS1-Cy3 and HS2-Cy5 contained split aptamer fragments of ATP and are labeled with a fluorescent donor (Cy3) and acceptor (Cy5), respectively. The RFDN integrated multiple split aptamer fragments and increased the local concentration of sensing probes. The binding of ATP to aptamer fragments on the RFDN shortened the distance between Cy3 and Cy5, resulting in obvious ratiometric signals (fluorescence resonance energy transfer). The RFDN showed good biocompatibility and can be internalized into cells in a caveolin-dependent endocytosis pathway. The co-localization imaging results indicated that the DNA nanostructure could target the mitochondria via Cy3 and Cy5. Moreover, the confocal imaging results showed that the intracellular ATP changes stimulated by drugs in living cells could be indicated by the RFDN. In this way, the RFDN is expected to be a simple, flexible, and general platform for chemo/biosensing in living cells.

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Multivalent Self-Assembled DNA Polymer for Tumor-Targeted Delivery and Live Cell Imaging of Telomerase Activity

Cited by 37 publications

References 29 publications

A Cooperatively Activatable, DNA‐based Fluorescent Reporter for Imaging of Correlated Enzymatic Activities

A Cooperatively Activatable, DNA‐based Fluorescent Reporter for Imaging of Correlated Enzymatic Activities

Orderly Assembled, Self-Powered FRET Flares for MicroRNA Imaging in Live Cells

Ratiometric Fluorescent DNA Nanostructure for Mitochondrial ATP Imaging in Living Cells Based on Hybridization Chain Reaction

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