Programming a DNA tetrahedral nanomachine as an integrative tool for intracellular microRNA biosensing and stimulus-unlocked target regulation

Yu, Lianyu; Yang, Sha; Liu, Zeyu; Qiu, Xiaopei; Tang, Xiaoqi; Zhao, Shuang; Xu, Hanqing; Gao, Mingxuan; Bao, Jing; Zhang, Ligai; Luo, Dan; Chang, Kai; Chen, Ming

doi:10.1016/j.mtbio.2022.100276

Cited by 14 publications

(12 citation statements)

References 60 publications

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“…DNA nanostructures have attracted comprehensive awareness as a multifunctional platform in applications of medicine and biology because of their excellent biocompatibility, unified size and appearances, and organizational structural fabricability. − Moreover, tetrahedral DNA nanostructures exhibit more drug loading and sustain drug release skills. Many kinds of diagnostic or therapeutic surrogates, like active proteins, chemotherapeutic drugs, imaging probes, and gene therapy agents, can be embedded within these nanostructures and sent to particular areas via the enhanced permeability and retention (EPR) effect. , Furthermore, functional moieties (including peptides, antibodies, and targeting aptamers) can be embellished on these agents to sustain the targeting property. Thus, these advantages make tetrahedral DNA more attractive as a nanoplatform for targeted delivery and drug loading.…”

Section: Introductionmentioning

confidence: 99%

“…Many kinds of diagnostic or therapeutic surrogates, like active proteins, chemotherapeutic drugs, imaging probes, and gene therapy agents, can be embedded within these nanostructures and sent to particular areas via the enhanced permeability and retention (EPR) effect. 21,22 Furthermore, functional moieties (including peptides, antibodies, and targeting aptamers) can be embellished on these agents to sustain the targeting property. Thus, these advantages make tetrahedral DNA more attractive as a nanoplatform for targeted delivery and drug loading.…”

Section: ■ Introductionmentioning

confidence: 99%

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Multifunctional DNA Tetrahedron for Alzheimer’s Disease Mitochondria-Targeted Therapy by MicroRNA Regulation

Peng

Mei

et al. 2023

ACS Appl. Mater. Interfaces

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The principal hallmark of Alzheimer’s disease (AD) is neuron mitochondrial dysfunction, whereas mitochondrial miRNAs potentially play important roles. Nevertheless, efficacious mitochondria organelle therapeutic agents for treatment and management of AD are highly advisable. Herein, we report a multifunctional DNA tetrahedron-based mitochondria-targeted therapeutic platform, termed tetrahedral DNA framework-based nanoparticles (TDFNs), which was modified with triphenylphosphine (TPP) for mitochondria-targeting, cholesterol (Chol) for crossing the central nervous system, and functional antisense oligonucleotide (ASO) for both AD diagnosis and gene silencing therapy. After injecting intravenously through the tail vein of 3 × Tg-AD model mice, TDFNs can both easily cross the blood brain barrier and accurately arrive at the mitochondria. The functional ASO could not only be detected via the fluorescence signal for diagnosis but also mediate the apoptosis pathway through knocking miRNA-34a down, leading to recovery of the neuron cells. The superior performance of TDFNs suggests the great potential in mitochondria organelle therapeutics.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Multifunctional DNA Tetrahedron for Alzheimer’s Disease Mitochondria-Targeted Therapy by MicroRNA Regulation

Peng

Mei

et al. 2023

ACS Appl. Mater. Interfaces

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“…D) Adapted with permission. [ 144 ] Copyright 2022, Elsevier Ltd. E) Schematic representation of aptamer/DNAzyme complexes for cancer‐related gene detection and regulation. Adapted with permission.…”

Section: Recent Delivery Strategies For Dnazyme Catalytic Improvementmentioning

confidence: 99%

“…In addition to target mRNA silencing, researchers have reported that DNAzymes, which bind to DNA tetrahedrons, could simultaneously detect miRNA content and regulate gene expression in cells. [ 144 ] Specifically, the P1, P2, P4, and P5 chains constitute the basic backbone of the DNA tetrahedron, and P5 contains the DNAzyme sequence, which can cut the P3 sequence (Figure 6D). This operation can separate the fluorescein amidites (FAM) fluorophore on the P3 sequence from the Black Hole Quencher‐1 dye (BHQ1) quencher to realize fluorescence imaging.…”

Section: Recent Delivery Strategies For Dnazyme Catalytic Improvementmentioning

confidence: 99%

Therapeutic DNAzymes: From Structure Design to Clinical Applications

et al. 2023

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Therapeutic DNAzymes have unceasingly intrigued the scientific community owing to their prosperous gene regulation capability. The efficacy of DNAzymes against many types of diseases has been extensively studied for over two decades. However, the high expectations for DNAzymes are still not translated to the clinic because of their low effectiveness in vivo. Over the last five years, several aspects have been considered to optimize DNAzyme‐integrated therapeutics, including structural stability, mechanism exploration, cell internalization rate, cofactor activation, and off‐target effects. Hence, this review first discusses the early monotherapy and structural design of DNAzymes. Subsequently, the latest modes of action are reviewed, followed by an elaboration on structural stabilization strategies considering the catalytic core and substrate‐binding arms. DNAzyme‐based synergistic therapy is then examined, highlighting responsive carrier construction, synergistic effects, the latest discovered advanced functions, and off‐target concerns. Beyond this, key clinical advances in DNAzyme‐based therapy are elucidated by showcasing clinical progress. Finally, future trends and development challenges for DNAzyme‐powered therapeutics in the coming years are discussed in detail.

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“…Benefiting from the specificity and thermodynamics of Watson–Crick base pairing rules, artificial DNA nanomachines combine the advantages of programmability, self-assembly, and predictability, and they have been applied in the smart detection/diagnosis of diseases or controllable drug release. − Wang et al proposed a well-directed three-dimensional walking nanomachine based on a DNA dendrimer track for the intracellular detection and imaging of microRNA (miRNA) . Miao et al.…”

Section: Introductionmentioning

confidence: 99%

Modular Engineering of a DNA Tetrahedron-Based Nanomachine for Ultrasensitive Detection of Intracellular Bioactive Small Molecules

Yang

Zhao

Wang

et al. 2023

ACS Appl. Mater. Interfaces

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Bioactive small molecules serve as invaluable biomarkers for recognizing modulated organismal metabolism in correlation with numerous diseases. Therefore, sensitive and specific molecular biosensing and imaging in vitro and in vivo are particularly critical for the diagnosis and treatment of a large group of diseases. Herein, a modular DNA tetrahedron-based nanomachine was engineered for the ultrasensitive detection of intracellular small molecules. The nanomachine was composed of three self-assembled modules: an aptamer for target recognition, an entropy-driven unit for signal reporting, and a tetrahedral oligonucleotide for the transportation of the cargo (e.g., the nanomachine and fluorescent markers). Adenosine triphosphate (ATP) was used as the molecular model. Once the target ATP bonded with the aptamer module, an initiator was released from the aptamer module to activate the entropy-driven module, ultimately activating the ATP-responsive signal output and subsequent signal amplification. The performance of the nanomachine was validated by delivering it to living cells with the aid of the tetrahedral module to demonstrate the possibility of executing intracellular ATP imaging. This innovative nanomachine displays a linear response to ATP in the 1 pM to 10 nM concentration range and demonstrates high sensitivity with a low detection limit of 0.40 pM. Remarkably, our nanomachine successfully executes endogenous ATP imaging and is able to distinguish tumor cells from normal ones based on the ATP level. Overall, the proposed strategy opens up a promising avenue for bioactive small molecule-based detection/diagnostic assays.

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Programming a DNA tetrahedral nanomachine as an integrative tool for intracellular microRNA biosensing and stimulus-unlocked target regulation

Cited by 14 publications

References 60 publications

Multifunctional DNA Tetrahedron for Alzheimer’s Disease Mitochondria-Targeted Therapy by MicroRNA Regulation

Multifunctional DNA Tetrahedron for Alzheimer’s Disease Mitochondria-Targeted Therapy by MicroRNA Regulation

Therapeutic DNAzymes: From Structure Design to Clinical Applications

Modular Engineering of a DNA Tetrahedron-Based Nanomachine for Ultrasensitive Detection of Intracellular Bioactive Small Molecules

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