In Situ Modulating DNAzyme Activity and Internalization Behavior with Acid-Initiated Reconfigurable DNA Nanodevice for Activatable Theranostic

Lei, Yanli; Tang, Jinlu; He, Xiaoxiao; Shi, Hui; Zeng, Yu; Sun, Hanjun; Wang, Kemin

doi:10.1021/acs.analchem.1c00426

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…The split of the DNAzyme sequences was based on our previous report. 35 As expected in schematic (Figure S6A), the free therapy unit HP was able to cut the substrate EGR-1 mRNA into small pieces upon addition of Zn 2+ ions (Figure S6B), which proved the reasonable design of the sequence. The results were further explored by fluorescence assays (Figure S6C).…”

Section: ■ Results and Discussionsupporting

confidence: 65%

Endogenous miRNA-Activated DNA Nanomachine for Intracellular miRNA Imaging and Gene Silencing

Ren

Wen

et al. 2021

Anal. Chem.

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The development of multifunctional nanoplatforms that integrate both diagnostic and therapeutic functions has always been extremely desirable and challenging in the cancer combat. Here, we report an endogenous miRNA-activated DNA nanomachine (EMDN) in living cells for concurrent sensitive miRNA imaging and activatable gene silencing. EMDN is constructed by interval hybridization of two functional DNA monomers (R/HP and F) to a DNA nanowire generated by hybridization chain reaction. After the target cell-specific transportation of EMDN, intracellular let-7a miRNA initiates the DNA nanomachine by DNA strand displacement cascades, resulting in an amplified fluorescence resonance energy-transfer signal and the release of many free HP sequences. The restoration of HP hairpin structures further activates the split-DNAzyme to identify and cleave the EGR-1 mRNA to realize gene silencing therapy. The proposed EMDN shows efficient cell internalization, good biological stability, rapid reaction kinetics, and the ability to avoid false-positive signals, thus ensuring reliable miRNA imaging in living cells. Meanwhile, the controlled activation of the split-DNAzyme activity regulated by the intracellular specific miRNA may be promising in the precise treatment of cancer. Collectively, this strategy provides a valuable nanoplatform for early clinical diagnosis and activatable gene therapy of tumors.

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Section: ■ Results and Discussionsupporting

confidence: 65%

Endogenous miRNA-Activated DNA Nanomachine for Intracellular miRNA Imaging and Gene Silencing

Ren

Wen

et al. 2021

Anal. Chem.

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“…Currently, many nanocarriers (e.g., DNA tetrahedron, AuNPs, etc.) have been considered to protect DNA probes from nuclease degradation [28–32] . Thus, we envisioned whether 3D carriers based on Exos also had a similar capability.…”

Section: Resultsmentioning

confidence: 99%

“…have been considered to protect DNA probes from nuclease degradation. [28][29][30][31][32] Thus, we envisioned whether 3D carriers based on Exos also had a similar capability. To prove this concept, we measured the fluorescence recovery of the self-quenched hairpin H2 modified with cholesterol (termed H2-FQ) that anchored onto Exos in 10 % ultracentrifuged (UC) serum (ie, Exosdepleted fetal bovine serum).…”

Section: Resultsmentioning

confidence: 99%

A Self‐Serviced‐Track 3D DNA Walker for Ultrasensitive Detection of Tumor Exosomes by Glycoprotein Profiling

Wang

Zeng

et al. 2022

Angewandte Chemie

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Sensitive and accurate analysis of low‐concentration of tumor‐derived exosomes (Exos) in biofluids is essential for noninvasive cancer diagnosis but is still challenging due to the lack of high‐sensitive methods with low‐cost and easy‐operation. Herein, exploiting target Exos as a three‐dimensional (3D) track for the first time, we developed a self‐serviced‐track DNA walker (STDW) for wash‐free detection of tumor Exos using exosomal glycoprotein, which was enabled by split aptamer‐recognition‐initiated autonomous running powered by a catalytic hairpin assembly (CHA). Benefiting from high selectivity and sensitivity of the STDW assay, direct detection of tumor Exos in cell culture medium and serum could also be realized. Furthermore, this method exhibited high accuracy in clinical sample analysis, offering the potential for early cancer diagnosis and postoperative response prediction.

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“…Subsequently, we continuously developed acid-responsive assembly of multivalent nanotheranostics systems based on activatable strategy and successfully used to realize contrast-enhanced imaging of cancer cells. One is acid-activated reconfiguration of DNAzyme-based multivalent theranostics nanodevice for cancer cells imaging and gene therapy 38 . The other is pH-driven in situ constructed of activatable multivalent theranostics platform for intracellular TK1 mRNA activated cancer cells imaging and killing 39 .…”

Section: Introductionmentioning

confidence: 99%

Acidic microenvironment triggered in situ assembly of activatable three-arm aptamer nanoclaw for contrast-enhanced imaging and tumor growth inhibition in vivo

Huang¹,

Wu²,

He³

et al. 2022

Theranostics

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Rationale: Static assembled multivalent DNA nanotheranostics system have encountered some bottleneck problems in cancer imaging and therapy, such as poor penetration and high immunogenicity. Herein, we proposed an acidic tumor microenvironment triggered assembly of activatable multivalent nanodevice, called “three-arm aptamer nanoclaw” (TA-aptNC), assembled from three pH-responsive aptamer-decorated DNA monomers (pH-aptDMs) to facilitate their functions of imaging and therapy. Methods: The activated TA-aptNC was constructed by acidic microenvironment triggered in situ assembly of three pH-aptDMs. Designer pH-aptDM was established based on the combination of a pH-responsive i-motif switch and an assembly module with a cell membrane anchoring aptamer ligand. Acidic microenvironment-triggered the assembly of the TA-aptNC was characterized by electrophoresis and atomic force microscopic (AFM). The binding affinity and stability of the TA-aptNC, comparing the monovalent pH-aptDM, were studied via the flow cytometry and nuclease resistance assays. Acidic microenvironment-activated contrast-enhanced tumor imaging and significantly antitumor efficiency were evaluated in vitro and in vivo . Results : At physiological pH environment, the pH-aptDMs with excellent tissue permeability exited as inactivated and monodispersed small monomer. When encountering acidic microenvironment at the tumor site, pH-responsive i-motif switch liberated from the pH-aptDMs, and the three unconstrained DNA modules (DM 1 , DM 2 and DM 3 ) subsequently assembled in situ into the TA-aptNC. Compared with monovalent pH-aptDMs, the spontaneously formed activatable TA-aptNC afforded 2-fold enhanced binding ability via the multivalent effect, which further facilitated the selective tumor cell uptake capability, thus enabling a contrast-enhanced tumor imaging and significantly antitumor efficiency in vivo without systemic toxicity. Conclusions : The proposed strategy offers valuable insight into excavating an endogenous stimuli-triggered assembly of multivalent nanodevice for accurate diagnosis and efficient tumor therapy.

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In Situ Modulating DNAzyme Activity and Internalization Behavior with Acid-Initiated Reconfigurable DNA Nanodevice for Activatable Theranostic

Cited by 7 publications

References 30 publications

Endogenous miRNA-Activated DNA Nanomachine for Intracellular miRNA Imaging and Gene Silencing

Endogenous miRNA-Activated DNA Nanomachine for Intracellular miRNA Imaging and Gene Silencing

A Self‐Serviced‐Track 3D DNA Walker for Ultrasensitive Detection of Tumor Exosomes by Glycoprotein Profiling

Acidic microenvironment triggered in situ assembly of activatable three-arm aptamer nanoclaw for contrast-enhanced imaging and tumor growth inhibition in vivo

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