DNA nanotriangle-scaffolded activatable aptamer probe with ultralow background and robust stability for cancer theranostics

Lei, Yanli; Qiao, Zhenzhen; Tang, Jinlu; He, Xiaoxiao; Shi, Hui; Ye, Xiaosheng; Yan, Lv’an; He, Dinggeng; Wang, Kemin

doi:10.7150/thno.24683

Cited by 40 publications

(35 citation statements)

References 37 publications

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“…Type of NS Imaging modality Applications [77] RNA nanostructure Fluorescence Delivery of miRNA-based therapeutics [79] DNA origami triangle Fluorescence Imaging and therapy of breast cancer [80] DNA nanotriangle Fluorescence Bioimaging and drug delivery of DOX [64] DNA octahedron Fluorescence Assessment of immune activation [83] Different 2D and 3D origami structure…”

Section: Reference Numbermentioning

confidence: 99%

“…Superior targeted binding affinity with an ultralow nonspecific background was observed, thus generating high contrast tumor imaging within an extended time window of 8 h. Moreover, as a consequence of a five‐time improvement in DOX loading capabilities in comparison to the control, the DNA nanotriangle‐scaffold aptamer demonstrated high antitumor efficacy in vivo with 81.95% inhibition and no observable bodyweight loss, therefore indicating favorable biocompatibility ( Figure ). [ 80 ] DNA dendrimers have also been developed as dual imaging and drug delivery platform. The nanostructures were assembled from three‐armed Y‐shaped DNA monomers using an enzyme‐free step‐by‐step base‐pairing assembly strategy.…”

Section: Introduction and Applications Of Dna Nanostructures And Dna‐mentioning

confidence: 99%

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DNA Nanostructures and DNA‐Functionalized Nanoparticles for Cancer Theranostics

et al. 2020

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Dedicated to the life and legacy of Moritz F. Kircher In the last two decades, DNA has attracted significant attention toward the development of materials at the nanoscale for emerging applications due to the unparalleled versatility and programmability of DNA building blocks. DNA-based artificial nanomaterials can be broadly classified into two categories: DNA nanostructures (DNA-NSs) and DNA-functionalized nanoparticles (DNA-NPs). More importantly, their use in nanotheranostics, a field that combines diagnostics with therapy via drug or gene delivery in an all-in-one platform, has been applied extensively in recent years to provide personalized cancer treatments. Conveniently, the ease of attachment of both imaging and therapeutic moieties to DNA-NSs or DNA-NPs enables high biostability, biocompatibility, and drug loading capabilities, and as a consequence, has markedly catalyzed the rapid growth of this field. This review aims to provide an overview of the recent progress of DNA-NSs and DNA-NPs as theranostic agents, the use of DNA-NSs and DNA-NPs as gene and drug delivery platforms, and a perspective on their clinical translation in the realm of oncology.

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Section: Reference Numbermentioning

confidence: 99%

Section: Introduction and Applications Of Dna Nanostructures And Dna‐mentioning

confidence: 99%

DNA Nanostructures and DNA‐Functionalized Nanoparticles for Cancer Theranostics

et al. 2020

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“…This platform exploited cell‐internalizing aptamers to accomplish cell‐type‐specific delivery, along with the fluorescence properties of RNA mimics of GFP as surrogates for other large RNA‐based payloads. To further improve the affinity and stability of aptamer‐based probes for in vivo applications, Lei et al designed a novel theranostic strategy of DNA nanotriangle‐scaffolded multivalent split activatable aptamer probe (NTri‐SAAP), which combines advantages of programmable self‐assembly, multivalent effect and target‐activatable architecture. The NTri‐SAAP increased doxorubicin loading capacity by ≈5 times, which further realized a high antitumor efficacy in vivo with 81.95% inhibition but no obvious body weight loss.…”

Section: Molecular Engineering Of Aptamer‐based Nanomaterials Toward mentioning

confidence: 99%

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

Zhang

Lan

2019

Adv Healthcare Materials

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equally exciting and perhaps more challenging field of application is toward their in vivo applications, including living animals and human bodies, in diverse areas, [2] such as sensing, drug delivery, medical imaging, and cancer therapy. However, most of these nanomaterials lack selectivity toward targets of interests. Therefore, to employ these nanomaterials for a wider range of in vivo applications, various molecular engineering approaches have been employed to obtained nanomaterials functionalized with biomolecules to enable selective targeting. [3][4][5] Among these biomolecules, functional nucleic acids, or FNAs, have shown the most promise.FNAs are DNA or RNA molecules that can interact with or bind to a specific analyte, resulting in a conformational change and/or a catalytic reaction. [6] As their names suggested, ribozymes and deoxyribozymes (called DNAzyme hereafter) can act as enzymes in the presence of cofactors to catalyze various reactions, including cleavage and ligation of RNA/DNA, and phosphorylation and peroxidation of DNA. On the other hand, riboswitches and DNA aptamers are antibody-like receptors that can bind target molecules with high affinity and selectivity. Furthermore, the binding abilities of riboswitches and aptamers can be combined with the enzymatic function of ribozymes or DNAzymes to form aptazymes so that the binding of targets can inhibit or enhance the catalytic activities. These nucleic acids, including DNAzymes, aptamers, and aptazymes, are collectively known as FNAs to emphasize their functions beyond the traditional genetic storage and transformations roles for DNA and RNA. Unlike DNA and RNA inside biological systems, FNAs are isolated via a combinatorial technique known as in vitro selection, or a process also known as systematic evolution of ligands by exponential enrichment (SELEX). The discovery of new functions of nucleic acids has not only resulted in major advances in the fields of molecular biology and biochemistry, but also revolutionized sensors designs for both in vitro and in vivo applications. [7,8] Over the past decade, numerous FNA-based nanomaterials have been developed. [9][10][11][12] Among these FNA-based nanosystems, the functions of FNAs can be categorized into two types: diagnostic function and therapeutic function. For the diagnostic function, the FNAs serve either as the biorecognition ligands for direct sensing and imaging of the Recent advances in nanotechnology and engineering have generated many nanomaterials with unique physical and chemical properties. Over the past decade, numerous nanomaterials are introduced into many research areas, such as sensors for environmental monitoring, food safety, point-ofcare diagnostics, and as transducers for solar energy transfer. Meanwhile, functional nucleic acids (FNAs), including nucleic acid enzymes, aptamers, and aptazymes, have attracted major attention from the biomedical community due to their unique target recognition and catalytic properties. Benefiting from the recent progress of molecular engine...

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“…They had a good enhancement effect in enhancing signal‐to‐background ratio and reducing nonspecific signal because of their excellent merit in avoiding steric hindrance. Thus, the application of split aptamer was various, such as biosensing, bioimaging, drug delivery, and theranostics …”

Section: Introductionmentioning

confidence: 99%

“…Thus, the application of split aptamer was various, such as biosensing, 5,6 bioimaging, 7 drug delivery, 8 and theranostics. 9 Understanding the interaction of split aptamer/vascular endothelial growth factor 165 (VEGF 165 ) was of great significance for the application of split aptamer. 10 Several methods have been exploited, including electrochemical methods, fluorescence spectroscopy, surface enhanced Raman scattering methods, 11 dynamic light scatting, 12 and surface plasmon resonance.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the interaction between split aptamer and vascular endothelial growth factor 165 using single molecule force spectroscopy

Zheng

Liu

et al. 2019

J of Molecular Recognition

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Understanding the binding of split aptamer/its target could become a breakthrough in the application of split aptamer. Herein, vascular endothelial growth factor (VEGF), a major biomarker of human diseases, was used as a model, and its interaction with split aptamer was explored with single molecule force spectroscopy (SMFS). SMFS demonstrated that the interaction force of split aptamer/VEGF165 was 169.44 ± 6.59 pN at the loading rate of 35.2 nN/s, and the binding probability of split aptamer/VEGF165 was dependent on the concentration of VEGF165. On the basis of dynamic force spectroscopy results, one activation barrier in the dissociation process of split aptamer/VEGF165 complexes was revealed, which was similar to that of the intact aptamer/VEGF165. Besides, the dissociation rate constant (koff) of split aptamer/VEGF165 was close to that of intact aptamer/VEGF165, and the interaction force of split aptamer/VEGF165 was higher than the force of intact aptamer/VEGF165. It indicated that split aptamer also possessed high affinity with VEGF165. The work can provide a new method for exploring the interaction of split aptamer/its targets at single‐molecule level.

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DNA nanotriangle-scaffolded activatable aptamer probe with ultralow background and robust stability for cancer theranostics

Cited by 40 publications

References 37 publications

DNA Nanostructures and DNA‐Functionalized Nanoparticles for Cancer Theranostics

DNA Nanostructures and DNA‐Functionalized Nanoparticles for Cancer Theranostics

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

Investigation of the interaction between split aptamer and vascular endothelial growth factor 165 using single molecule force spectroscopy

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