A smart multiantenna gene theranostic system based on the programmed assembly of hypoxia-related siRNAs

Gong, Xue; Wang, Haizhou; Li, Ruomeng; Tan, Kaiyue; Wei, Jie; Wang, Jing; Chen, Hong; Shang, Jinhua; Liu, Xiaoqing; Liu, Jing; Wang, Fuan

doi:10.1038/s41467-021-24191-9

Cited by 48 publications

(28 citation statements)

References 53 publications

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“…The booming development of nanotechnology supplements a versatile and promising toolbox for metastasis inhibition. ,− Indeed, various nanostructured platforms have been assembled for antimetastasis therapy, including micelles, lipids, proteins, polymers, and inorganic nanoparticles. ,− These metastasis-targeting nanomedicines have significantly expanded from small-molecule chemotherapeutic drugs or small-molecule inhibitors (e.g., receptor tyrosine kinase inhibitors) to peptides/antibody inhibitors , (e.g., integrin inhibitors, immune-checkpoint inhibitors) and smart nucleic acid drugs ,− (siRNA and antisense). Among these, therapeutic nucleic acid drugs show great potential for antimetastasis studies and have received increasing attention recently due to their intrinsic biocompatibility and easy synthesis.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional DNAzyme-Anchored Metal–Organic Framework for Efficient Suppression of Tumor Metastasis

Zhao

Sun

et al. 2022

ACS Nano

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High mortality and rapid development of metastasis requires the development of more effective antimetastasis strategies. However, conventional therapeutic methods, including surgery, radiation therapy, and chemotherapy, show less effectiveness in curbing the metastatic spread of cancer cells and the formation of metastases. A therapeutic platform, targeting the early stage of metastasis cascade, could effectively prevent metastasis dissemination. Herein, Fe/Mn-based metal–organic frameworks (FMM) were constructed for the delivery of a specific DNAzyme with high catalytic cleavage activity on the metastasis-involved Twist mRNA, thus efficiently inhibiting the invasion of cancer cells through DNAzyme-catalyzed gene silencing. Highly potent combined gene/chemodynamic therapy is achieved from the self-supplied DNAzyme cofactors and efficient glutathione depletion. Importantly, by virtue of the intrinsic photo-to-thermal conversion of the FMM nanocarriers, our combined therapeutic strategy could be further promoted under photothermal stimuli to speed up the Fenton reaction and to accelerate the release of the Twist DNAzyme with efficient gene therapy. Consequently, the effective elimination of tumors and the blockage of metastasis are simultaneously achieved under photothermal/magnetic resonance imaging guidance. This work aims at developing versatile theranostic agents to combat metastatic tumors.

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Section: Introductionmentioning

confidence: 99%

Multifunctional DNAzyme-Anchored Metal–Organic Framework for Efficient Suppression of Tumor Metastasis

Zhao

Sun

et al. 2022

ACS Nano

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“…The natural exosome modules, denoted as human umbilical cord mesenchymal stem cells (HUMSCs)‐derived exosome (MSCEXO), were obtained by well‐established ultracentrifugation method from HUMSCs. [ 16 ] The morphology and size distribution of the natural exosome module were observed by transmission electron microscopy (TEM) and nanoparticle tracing analysis (NTA), which displayed a typical sphere morphology with diameter around 143 nm (Figures S1 and S2, Supporting Information). Furthermore, western blot analysis confirmed the existence of common exosome biomarkers, such as tetraspanins CD63 and CD81.…”

Section: Resultsmentioning

confidence: 99%

Engineered Exosomes with Independent Module/Cascading Function for Therapy of Parkinson's Disease by Multistep Targeting and Multistage Intervention Method

Wang

Yang

et al. 2022

Advanced Materials

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process due to the aggressivity (e.g., electroporation or sonication methods), low yield, or poor controllability of traditional methods. [2,3] In addition, because the separation process from donor cells involves cumbersome processing steps, the weakened or lost function of exosomes in this process is difficult to be enhanced or compensated in the process of engineering. [4] In this work, the concept of "independent module/cascading function" is proposed for the controllable construction of engineered exosomes, that is, nanosized artificial module with specific functions is synthesized independently, and then selectively and controllably combined with natural exosome module in a "one-by-one" way to construct engineered exosome. The concept of "independent module" is not limited by the activity conditions of exosomes, so as to greatly enrich the preparation methods and types of artificial modules. Meantime, based on the selective and controllable combination technology between different modules, this method can effectively protect the integrity of exosome membrane structure and the activity of functional proteins and nucleic acids on membrane surface. "Cascading function" refers to endowing exosomes with new functions through rich design of artificial modules, and meeting the complex requirements of disease treatment through cascading effect, so as to play a remarkable therapeutic effect.In addition, this kind of engineered exosomes is applied to the treatment of Parkinson's disease (PD), aiming to solve the challenges of precise targeting and complex needs of PD treatment, of which the pathogenesis is complex and involves many factors and there is no effective method to completely cure it. [5] Up to now, the pathogenesis of PD can be summarized as the following process: nuclear gene mutation of dopaminergic neurons inhibits the normal hydrolysis of α-synuclein (α-syn) and promotes its aggregation in mitochondria, producing high concentration of reactive oxygen species (ROS), which further leads to enhanced expression of inducible nitric oxide synthase (iNOS) and neuroinflammation, and destroys itself and its surrounding neuronal cells. [6] Exosomes derived from stem cells have the potential to promote tissue repair and nerve regeneration, and have the ability to penetrate the blood-brain barrier Current exosome engineering methods usually lead to the damage of exosome morphology and membrane, which cannot meet the complex needs of disease treatment. Herein, the concept of an "independent module/cascading function" is proposed to construct an engineered exosome nanotherapy platform including an independent artificial module and a natural module. The artificial module with movement/chemotaxis function is first synthesized, and then it is controllably combined with the natural exosome module with "one by one" mode through a "differentiated" modification method. The whole process can not only maintain the activity of the natural exosome module, but also endows it with motion ability, so as to realize the purpose of...

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“…[81][82][83][84][85][86] Ingenious 2D and 3D DNA structures, [87][88][89][90][91] switches, [92][93] DNA machines, [94][95][96][97] and nucleic acid-based materials of switchable properties [98][99][100] were designed. Diverse applications of the triggered structural motives of DNA were introduced, including the development of sensors [101][102][103][104] and amplified sensing machineries, [105][106][107] the engineering of stimuli-responsive drug carriers for nanomedicine and therapeutic applications, [108][109] the synthesis of stimuli-responsive hydrogels revealing shape-memory [110][111] and self-healing [112] functions and the engineering of nanopore channels for selective transport. [113] Particularly, the reconfiguration of nucleic acid structures has been used to develop dynamic DNA networks and circuitries.…”

Section: Introductionmentioning

confidence: 99%

Transient Out‐of‐Equilibrium Nucleic Acid‐Based Dissipative Networks and Their Applications

Wang

Willner

2022

Adv Funct Materials

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Dynamic, dissipative reactions play important roles in biological processes, and emulating such biological processes by artificial circuits and networks is a challenging topic in the area of Systems Chemistry. The present article summarizes efforts to apply the information encoded in the base sequence of nucleic acids to assemble transient, dissipative DNA‐based networks mimicking natural processes. The design principles of the transient nucleic acid‐based systems are introduced. Triggered reaction moduli lead to a transient intermediary constituent recovered to the parent moduli by enzymes, DNAzyme, or light as control units are described. Transient DNA‐based circuitries of enhanced complexities revealing temporal gated or cascaded transformations are demonstrated. Different applications of dynamically triggered transient circuits are introduced, including the temporal aggregation and deaggregation of plasmonic nanoparticles or semiconductor quantum dots and the control over their optical properties, the transient release and uptake of loads by aptamer scaffolds, and the transient reconfiguration of constitutional dynamic networks and the control over emergent catalytic functions. The future perspectives of dissipative nucleic acid‐based networks and their potential future applications are discussed.

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A smart multiantenna gene theranostic system based on the programmed assembly of hypoxia-related siRNAs

Cited by 48 publications

References 53 publications

Multifunctional DNAzyme-Anchored Metal–Organic Framework for Efficient Suppression of Tumor Metastasis

Multifunctional DNAzyme-Anchored Metal–Organic Framework for Efficient Suppression of Tumor Metastasis

Engineered Exosomes with Independent Module/Cascading Function for Therapy of Parkinson's Disease by Multistep Targeting and Multistage Intervention Method

Transient Out‐of‐Equilibrium Nucleic Acid‐Based Dissipative Networks and Their Applications

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