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ANALYTICAL CHEMISTRY · 2020 · IF 6.785

Deformation-Mediated Translocation of DNA Origami Nanoplates through a Narrow Solid-State Nanopore

Libo Zhu,Zhen Zhang,Quanjun Liu

With the development in DNA self-assembly technology, DNA origami nanostructures have been widely applied in biomedical research. Solid-state nanopores represent an emerging single-molecule sensing platform for studying nanostructures with arbitrary dimensions and physical characteristics, including DNA origami. Here, we employed relatively narrow silicon nitride nanopores to detect the deformation and translocation of DNA origami nanoplates with dimensions of approximately 60 × 54 nm. We performed translocation experiments using three nanopore diameters that are all smaller than the plat dimensions. Analysis of current blockade signals and the representative events reveals three types of translocation orientations for the nanoplates. Furthermore, by studying the electrical signal characteristics (current change and dwell time) for the different diameter pores, we obtained information about the translocation behaviors for the DNA nanoplates through different constrictions. Our investigation provides an approach to analyze the deformation and translocation of DNA origami structures.

CAS / MDL: 7447-40-7
研究领域: 生物物理学 · 纳米技术 · 单分子检测
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

QKCMP peptide carrier macromolecule structure and release system based on triangular DNA origami nanostructures: A novel strategy for promoting angiogenesis

Haifeng Wang,Yi Huang,Chenhui Zhou,Fanyong Gong,Jianyong Wang,Hao Liu,Wenhui Zhao,Yuxiang Zhao,Xiang Gao

In recent years, the use of nanocarriers to deliver bioactive peptides has become a new strategy to promote angiogenesis. The aim of this study was to develop a QKCMP peptide delivery system based on triangular DNA origami nanostructure (tDONs) carrier to improve the bioactivity and targeting of the peptide. The main objective of this study was to design and prepare QKCMP peptide-TDOns complexes and to evaluate their angiogenesis promoting effects in vitro and in vivo. tDONs were synthesized and purified, and then QKCMP peptide was loaded into tDONs. A variety of characterization techniques were used to evaluate the physicochemical properties of the complexes, including particle size, morphology, and RNA release efficiency. The effects of QKCMP peptid-TDons on proliferation, apoptosis, migration and angiogenesis of human umbilical vein endothelial cells (HUVEC) were evaluated by CCK8, EdU, Annexin V-FITC/PI, PI staining and Transwell assay. At the same time, its promoting effect on angiogenesis was further verified in zebrafish and mouse models. The successful preparation of QKCMP peptide-TDONS showed good biocompatibility and stability. The results of in vitro experiments showed that QKCMP peptide-TDons significantly promoted HUVEC proliferation, inhibited apoptosis, and activated endothelial cell function. Zebrafish experiments showed that QKCMP peptid-TDons effectively enhanced angiogenesis and promoted rapid repair of carotid vascular endothelium in mouse models.

CAS / MDL: 51805-45-9
研究领域: 生物医学工程 · 分子生物学 · 纳米医学
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BIOSENSORS & BIOELECTRONICS · 2019 · IF 9.518

A “time-frozen” technique in microchannel used for the thermodynamic studies of DNA origami

Peng Huang,Jingwen Wang,Long Jiao,Dandan Gu,Shusen Jiang,Mingpo Li,Wenlong lv,Hong Chen,Hao Pei

The emergence of DNA origami greatly accelerated the development of DNA nanotechnology. A thorough understanding of origami thermodynamics is very important for both fundamental studies and practical applications. These thermodynamic transitions usually take place in several seconds or even less, and are very difficult to monitor by conventional methods. Numerous tests are required to characterize the origami molecule's behaviors at different temperatures, which is very labor-intensive and time-consuming. In this paper, an axially distributed temperature gradient along a capillary was formed in a spatially varying temperature field. In such a temperature gradient, the origami molecule's thermodynamic processes occur and remain stable at every position along the capillary's microchannel . It looks like the time of the thermodynamic process is frozen along the microchannel. With this method, the origami molecule's thermodynamic characteristics at different temperatures can be obtained in a single experiment, and rapid processes can be monitored with ease by conventional methods for an adequate time period at low cost. In order to show its potential abilities, this method has been demonstrated in applications which the origami's assembly, denaturation and strand displacement are carry out in a flowing or stationary solution.

研究领域: 生物物理学 · 纳米技术 · 分子生物学
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

DNA origami-based composite nanosandwich for iteratively potentiated chemo-immunotherapy

Mengyue Li,Hanxi Zhang,Peizheng Xiong,Yuhan He,Wanyi Zhou,Chunhui Wu,Xiaoling Liao,Wei Zhang,Hong Yang,Yiyao Liu

Developing effective nanoplatforms for chemo-immunotherapy to achieve enhanced tumor suppression and systemic antitumor immunity has recently received extensive attention. Herein, we formulated a multifunctional DNA sandwich nanodevice, DSWAC/siPD-L1, based on triangular DNA origami, to implement enhanced cancer chemo-immunotherapy. Taking advantage of the tumor-targeting ability of the AS1411 aptamer, DSWAC/siPD-L1 efficiently delivered doxorubicin (DOX), CpG, and siPD-L1 into tumor cells. Moreover, the sandwich cavity spatially protects siPD-L1 from degradation, and the featured design of the DNA/RNA duplex linkers ensures effective intracellular release of siPD-L1. The pH-responsive release of cytotoxic DOX induces apoptosis and initial mild immunogenic cell death of tumor cells, presenting antigens to enhance the maturation of dendritic cells (DCs) with the assistance of the immune adjuvant CpG, thereby activating cytotoxic T lymphocytes to amplify antitumor immunity. Simultaneously, siPD-L1 downregulated the endogenous expression of PD-L1 to inhibit adaptive tumor immune escape. DSWAC/siPD-L1 initiated the iterative revolution of the cancer-immunity cycle, leading to the inhibition of primary and metastatic tumors, as demonstrated by DC maturation and T-cell infiltration in established subcutaneous primary tumor model and metastatic lung tumor model. Furthermore, the superior antitumor effect of DSWAC/siPD-L1 resulted in approximately 91 % inhibition of primary tumor growth and 93 % prevention of lung metastasis. Collectively, this study describes a siPD-L1-based sandwich DNA nanodevice functionalized with AS1411/CpG for enhanced cancer chemo-immunotherapy, inspiring the creation of more innovative drug nanocarriers and the exploitation of novel cancer therapies.

CAS / MDL: 25316-40-9
研究领域: 纳米医学 · 肿瘤学 · 分子生物学
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

DNA Origami–Anthraquinone Hybrid Nanostructures for In Vivo Quantitative Monitoring of the Progression of Tumor Hypoxia Affected by Chemotherapy

Yun Zeng,Peng Chang,Jingwen Ma,Ke Li,Chunhong Zhang,Yingying Guo,Hanrui Li,Qingxia Zhu,Huifang Liu,Wenjing Wang,Yuwei Chen,Dan Chen,Xu Cao,Yonghua Zhan

Hypoxia is a well-known feature of malignant solid tumors. To explain the misinterpretation of tumor hypoxia variation during chemotherapy, we developed a DNA origami-based theranostic nanoplatform with an intercalated anticancer anthraquinone as both the chemotherapeutic drug and the photoacoustic contrast agent. The size distribution of the DNA origami nanostructure is 44.5 ± 2.3 nm, whereas the encapsulation efficiency of the drug is 90.7 ± 1.0%, and the drug loading content is 92.2 ± 0.1%. The controlled cumulative release rates were measured in vitro, showing an acidic environment induced rapid drug release. The values of free energy of binding between the drugs and the DNA double helix were calculated through molecular simulations. The cell viability assay was used to characterize cytotoxicity, and fluorescence confocal cell imaging illustrates the biodistribution of the probe in vitro. Photoacoustic and fluorescence imaging were used to indicate drug delivery, release, and biodistribution to predict the drug’s chemotherapeutic effect in vivo, whereas the photoacoustic signals were compared with those of deoxygenated/oxygenated hemoglobin to represent the tissue hypoxia/normoxia maps during the chemotherapeutic process and indicate alleviated tumor hypoxia. Staining of tissue sections taken from organs and tumors was used to verify the results of photoacoustic imaging. Our results suggest that photoacoustic imaging can visualize this DNA origami-based theranostic nanoplatform and reveal the mechanisms of chemotherapy on tumor hypoxia.

CAS / MDL: 108-00-9 108-88-3
研究领域: 生物医学工程 · 癌症研究 · 分子生物学 · 诊疗学
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CHEMICAL RESEARCH IN CHINESE UNIVERSITIES · 2019 ·Vol. 36 ·期 2 ·254-260 · IF 1.071

Multivalent Aptamer-modified DNA Origami as Drug Delivery System for Targeted Cancer Therapy

Cao Mengyao,Sun Yueyang,Xiao Mingshu,Li Li,Liu Xiaohui,Jin Hong,Pei Hao

In spite of great development in nanoparticle-based drug delivery systems(DDSs) for improved therapeutic efficacy, it remains challenging for effective delivery of chemotherapeutic drugs to targeted tumor cells. In this work, we report a triangle DNA origami as targeted DDS for cancer therapy. DNA origami shows excellent biocompatibility and stability in cell culture medium for 24 h. In addition, the DNA origami structures conjugated with multivalent aptamers enable for efficient delivery of anticancer drug doxorubicin(Dox) into targeted cancer cell due to their targeting function, reducing side effects associated with nonspecific distribution. Moreover, we also demonstrated that the multivalent aptamer-modified DNA origami loading Dox exhibits prominent therapeutic efficacy in vitro . Accordingly, this work provides a good paradigm for the development of DNA origami nanostructure-based targeted DDS for cancer therapy.

CAS / MDL: 7558-80-7
研究领域: 纳米医学 · 癌症生物学 · 分子生物学
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ANALYTICA CHIMICA ACTA · 2025 · IF 6

Rational design of a 3D DNA origami cube as an ideal signal carrier for glass nanopore-based biosensors

Jiahai Wang,Jianji Zhu,Yunhui Li,Cenlin Gui,Baian Zhu,Zhuobin Zhu,Daqi Chen

Enhancing the signal-to-noise ratio (SNR) has long been a focus of research in the development of nanopore sensors. Herein, a 3D DNA origami cube with adjustable rigidity that exhibits exceptional selectivity and an ultra-high SNR exceeding 100 is designed and optimized. The assembly of this 3D DNA origami cube relies on a single scaffold strand derived from target DNA/RNA, as well as multiple staple strands. This construction process ensures that the cube only forms in the presence of the target DNA/RNA, thereby providing a highly sensitive and specific detection strategy. Without any intermediate steps, DNA amplicons amplified from a plasmid containing the S gene of the Omicron variant of SARS-CoV-2 were successfully transformed into 3D DNA origami cubes in the presence of staple strands in a one-pot reaction process. Nanopore counting of 3D DNA origami cubes, instead of the direct detection of the target gene, significantly ameliorates the interference effect from non-target subjects possessing a similar size and charge. This approach features an ultra-low detection limit of 50 aM, with a broad detection range from 50 aM to 50 pM, even in commercial buffers that contain large amounts of enzymes, stable proteins, and other non-target DNA sequences. Moreover, the DNA origami cube has a thermal stability of up to 70°C, which allows it to be used in a wide range of scenarios, including harsh conditions. We aim to extend this approach to detect many other targets and to integrate it into broader diagnostic toolkits. Nevertheless, given space constraints, not all possible applications could be thoroughly explored within this study.

研究领域: 生物物理学 · 纳米技术 · 分子诊断学
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BIOSENSORS & BIOELECTRONICS · 2022 · IF 12.545

Self-assembled DNA origami-based duplexed aptasensors combined with centrifugal filters for efficient and rechargeable ATP detection

Xiaojuan Wang,Zefeng Mao,Ruipeng Chen,Shuning Li,Shuyue Ren,Jun Liang,Zhixian Gao

DNA origami technology has great potential for biosensor applications. Here, we described the construction of a self-assembled DNA origami biosensor for the precise localization of fluorescent aptamers . Due to the molecular weight difference between DNA origami and aptamer, centrifugal filters were used to quantitatively detect adenosine triphosphate (ATP). The ATP-specific aptamer labeled with fluorescence reporter 6-carboxyfluorescein FAM (FAM-aptamer) was selected as the recognition element and signal probe . ATP duplexed aptamers bound to triangular DNA origami by base-complementary pairing, resulting in high fluorescence signals on the origami arrays. The competitive binding of ATP toward the FAM-aptamer triggered the release of FAM-aptamer-ATP complexes from the surface of the origami array, resulting in weakened fluorescence signals. For ATP quantification, 100 kD centrifugal filters were employed, followed by measurement of the fluorescence signal trapped on the origami arrays of the filter device. The successful synthesis of origami-aptamer arrays was characterized by atomic force microscopy , laser confocal microscopy , and electrophoresis . Fluorescence measurements exhibited an excellent linear relationship with logarithms of ATP concentrations within 0.1–100 ng mL −1 , with a detection limit of 0.29 ng mL −1 . By replacing aptamers and complementary strands, we demonstrated the potential of this method for 17β-estradiol detection. Considering that the detection mechanism is based on the hybridization and displacement of DNA strands, the detection system had the potential for recharging. Our study provides new insights into applying DNA origami technology in small molecule detection.

研究领域: 生物传感器 · 纳米技术 · 分子生物学 · 分析化学
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International Journal of Intelligent Robotics and Applications · 2018 ·Vol. 2 ·期 4 ·445-453 · IF 0

Nano-assembly and welding of gold nanorods based on DNA origami and plasmon-induced laser irradiation

Liu Yanting,Liu Yang,Shen Yajing

The bottom-up organization of noble metal nanostructures with nanometer-scale precision is an important goal in nanotechnology. Owing to their unique localized surface plasmon resonance, well-defined metal nanostructures arrays could be used to develop applications in nano-photonics, nano-plasmonics, and nano-electronics. This article proposes an alternative pathway of a controllable approach to assemble and weld together the gold nanostructures. As a typical plasmonic nanostructure, the gold nanorods (Au NRs) was synthesized by the classical seed-mediated growth method. Based on the recognition of biomolecules through complementary DNA hybridization, we used DNA origami strategy for controllable assembly of Au NRs. Rectangular DNA origami as a template can induce the geometrically assembled of Au NRs. We designed and fabricated tip-to-tip Au NRs dimers on the DNA templates. Then,the follow-up formation of nanojunctions between assembled tip-to-tip Au NRs dimers Au NRs was conducted by irradiating infrared femtosecond pulses laser. The ability to coupling plasmonic nanostructures by assembly and nano-welding could be fundamental to developing novel optical properties and ensuring materials.

CAS / MDL: 151-21-3
研究领域: 纳米技术 · 光子学 · 等离激元学 · 材料科学
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ACS Nano · 2023 · IF 17.1

Virus Mimetic Framework DNA as a Non-LNP Gene Carrier for Modulated Cell Endocytosis and Apoptosis

Qian Shi,Yuanyuan Wu,Yunyun Xu,Min Bao,Xiao Chen,Kui Huang,Qiulan Yang,Yang Yang

Mimicking the size and shape of spherical viruses, we constructed a soccer-ball shaped virus-inspired DNA origami (ViDO) framework as a programmable non-LNP (lipid nanoparticle) gene carrier. The DNA framework was decorated with precisely controlled recognition molecules outside and loaded with adequate genetic molecules inside. Five variants were constructed to systematically investigate their cell uptake and modulated gene silencing efficiency. Cellular uptake was enhanced with an increasing number of aptamers, while with a median number of aptamer supply, dispersed distribution performed better than the clustered pattern. Intriguingly, the transfection efficiency was maximized using the ViDO with clustered five aptamers, which exhibited a competitive RNA silencing effect induced by Lipo2000 with low cytotoxicity. Our results revealed the effects of aptamer distribution patterns on endocytosis and transfection, thus providing a programmable platform for meticulous optimization of the gene delivery system.

CAS / MDL: 128446-34-4
研究领域: 分子生物学 · 纳米技术 · 基因工程 · 生物医学工程
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JOURNAL OF NANOBIOTECHNOLOGY · 2023 ·Vol. 21 ·期 1 ·1-14 · IF 10.2

NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy

Li Mengyue,Yang Geng,Zheng Yue,Lv Jiazhen,Zhou Wanyi,Zhang Hanxi,You Fengming,Wu Chunhui,Yang Hong,Liu Yiyao

Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier’s endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.

CAS / MDL: 25316-40-9
研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 分子生物学 · 药学 · 成像技术
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JOURNAL OF HAZARDOUS MATERIALS · 2023 · IF 13.6

DNA origami-mediated plasmonic dimer nanoantenna-based SERS biosensor for ultrasensitive determination of trace diethylstilbestrol

Sen Li,Baodi Shi,Defu He,Huanying Zhou,Zhixian Gao

Diethylstilbestrol (DES) is a threatening factor to the human endocrine system. Here, we reported a DNA origami-assembled plasmonic dimer nanoantenna-based surface-enhanced Raman scattering (SERS) biosensor for measuring trace DES in foods. A critical factor influencing the SERS effect is interparticle gap modulation of SERS hotspots with nanometer-scale accuracy. DNA origami technology aims to generate naturally perfect structures with nano-scale precision. Exploiting the specificity of base-pairing and spatial addressability of DNA origami to form plasmonic dimer nanoantenna, the designed SERS biosensor generated electromagnetic-enhancement and uniform-enhancement hotspots to improve sensitivity and uniformity. Owing to their high target-binding affinity, aptamer-functionalized DNA origami biosensors transduced the target recognition into dynamic structural transformations of plasmonic nanoantennas, which were further converted to amplified Raman outputs. A broad linear range from 10 −10 to 10 −5 M was obtained with the detection limit of 0.217 nM. Our findings demonstrate the utility of aptamer-integrated DNA origami-based biosensors as a promising approach for trace analysis of environmental hazards.

研究领域: 纳米技术 · 生物传感 · 分析化学 · 环境科学
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