Acta Biomaterialia
·
2025
·
IF 9.6
Chunfa Chen,Quan Li,Beinuo Wang,Qian Liu,Zi Wang,Bihang Zhang,Lu Wang,Yujuan Zou,Ziye Mou,Chengshan Ren,Zaichun You,Bin Wang,Zhi Xu,Hang Qian
Acute lung injury (ALI) is characterized by widespread inflammation and oxidative stress, leading to impaired gas exchange and significant morbidity. In this study, we propose a potential approach using a magnesium-free DNA self-assembly strategy to assemble a DNA nanotube that carries agmatine and microRNA-126b mimics (NT AGM -126). Agmatine not only reduces electrostatic repulsion between DNA helices, thereby facilitating the folding of the DNA nanotube, but also serves as a drug that inhibits iNOS signaling. The microRNA-126b mimics restore the downregulated microRNA-126b in macrophages and suppress inflammation by targeting high mobility group box 1 (HMGB1). Preliminary results indicated that agmatine can effectively facilitate the assembly of the DNA nanotube, improve serum stability, and enhance the cellular uptake efficiency of NT AGM -126. Further in vitro and in vivo results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation by downregulating iNOS and HMGB1, providing a combined therapeutic effect in ALI. This study highlights the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform for treating inflammatory diseases, broadening the application of DNA nanotechnology in biomedical research. Statement of Significance This study introduces a promising therapeutic approach using a magnesium-free DNA self-assembly strategy to create a DNA nanotube (NT AGM -126) that carries agmatine and microRNA-126b mimics. The agmatine not only aids in the assembly and stability of the DNA nanotube but also inhibits iNOS signaling, while the microRNA-126b mimics restore downregulated microRNA-126b in macrophages and suppress inflammation by targeting HMGB1. Preliminary and further results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation, providing a synergistic therapeutic effect in ALI. This study underscores the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform, broadening the application of DNA nanotechnology in the treatment of inflammatory diseases and advancing biomedical research.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Zheng Zhang,Tian Zhu,Yang Li,Bin Yu,Haiteng Tao,Haibo Zhao,Bo Cui
As the adsorption receptor of bacteriophage tail protein, bacterial lipopolysaccharide (LPS) is a main culprit responsible for nonalcoholic fatty liver disease (NAFLD) caused by high-fat diets. However, few studies have focused on how the interaction between intestinal bacteriophages and bacterial LPS affects the development and progression of NAFLD. Herein, we determined that excessive fat intake significantly increases the levels of endogenous LPS, while the administration of beneficial metabolites of the intestinal microbiota (specifically butyrate) alleviated hepatic injury in rats. The beneficial mechanism of butyrate was attributed to the reprogramming of the structure of the intestinal DNA virome (primarily, phageome). Butyrate possesses the potential to augment bacteriophagic microbial diversity, thereby potentially facilitating interactions between intestinal bacteriophages and bacterial LPS (in the case of homologous phage), further improving mitochondrial dysfunction and reactive oxygen species production, which, in turn, lowered HepG2 cell damage. Likewise, fecal phage transplantation further confirmed that intestinal phages from rats that received butyrate could effectively interact with bacterial LPS to reduce liver damage in rats. Taken together, modifying the intestinal phageome is a promising treatment option for high-fat diet-related NAFLD.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2016
·
IF 4.758
Huanshun Yin,Zhiqing Yang,Haiyan Wang,Yunlei Zhou,Shiyun Ai
A simple and sensitive electrochemical biosensor was fabricated for hydroxymethylated DNA detection and T4 β-glucosyltransferase activity assay based on the glycosylation of hydroxymethylated DNA and Hpa II restriction endonuclease system triggering signal amplification. After immobilizing double-stranded DNA (dsDNA) on the surface of carboxyl functionalized Fe 3 O 4 nanoparticle, the glycosylation reaction of hydroxymethylated cytosine can be performed with the catalytic effect of T4 β-glucosyltransferase using uridine diphosphoglucose as glucose donor. Then, 4-mercaptophenylboronic acid (4-MPBA) can be further reacted with glucose and captured on Fe 3 O 4 nanoparticle surface. After the dsDNA was digested by Hpa II, the fragment with 4-MPBA can be released from Fe 3 O 4 nanoparticle surface. After magnetic separation, this fragment can be further modified on gold electrode surface through the interaction between Au and −SH, which can result in a decreased electrochemical signal of [Fe(CN) 6 ] 3− . According to this detection strategy, the electrochemical biosensor showed high sensitivity with the low detection limits of 0.14 nM and 0.27 unit/mL for hydroxymethylated DNA and T4 β-glucosyltransferase. The fabricated biosensor also presented high selectivity and acceptable reproducibility. In addition, the inhibition activity of 4-phenylimidazole towards T4 β-glucosyltransferase was also investigated. This work provides a novel platform for hydroxymethylated DNA detection, T4 β-glucosyltransferase activity assay and its inhibition screening.
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RSC Advances
·
2014
·Vol. 4
·期 57
·29968-29974
·
IF 3.708
Yongjuan Wang,Yuming Zhou,Tao Zhang,Man He,Xiaohai Bu
This work describes a facile approach for the delaminating of Ni–In-layered double hydroxides (LDHs) by the intercalation of acetate anions in the LDHs gallery using co-precipitation method. The acetate-intercalated Ni–In LDHs exhibited swelling behavior in water and delaminated into semitransparent suspensions on the action of water. The transmission electron microscopy (TEM) and atomic force microscopic (AFM) observations revealed the formation of unilamellar LDHs nanosheets. This simple method did not need reflux at high temperatures, overcoming the deficiency of using organic solvents, resulting in a steady colloidal suspension of 2D nanosheets. The unique properties of 2D ultrathin nanosheets with full access to the positively charged activity sites make them attractive in terms of the improvement of DNA adsorption. The effect of dosage on the adsorption of DNA and the adsorption isotherm were investigated in detail. The equilibrium data were found to be well described by both the Langmuir and Freundlich models. Based on the mechanism of adsorption, the adsorption sites of exfoliated nanosheets can be easily occupied by highly negatively charged small anions through electrostatic interactions. The adsorbed DNA can be released via the addition of a hydrogen phosphate solution.
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Frontiers of Chemical Science and Engineering
·
2021
·Vol. 15
·期 6
·1572-1582
·
IF 4.204
Wu Shuyao,Sui Chengquan,Wang Chong,Wang Yulu,He Dongqing,Sun Ying,Zhang Yu,Meng Qingbo,Ma Tianyi,Song Xi-Ming
High density and uniform distribution of the gold nanoparticles functionalized single-stranded DNA modified reduced graphene oxide nanocomposites were obtained by non-covalent interaction. The positive gold nanoparticles prepared by phase inversion method exhibited good dimensional homogeneity and dispersibility, which could readily combine with single-stranded DNA modified reduced graphene oxide nanocomposites by electrostatic interactions. The modification of single-stranded DNA endowed the reduced graphene oxide with favorable biocompatibility and provided the preferable surface with negative charge for further assembling of gold nanoparticles to obtain gold nanoparticles/single-stranded DNA modified reduced graphene oxide nanocomposites with better conductivity, larger specific surface area, biocompatibility and electrocatalytic characteristics. The as-prepared nanocomposites were applied as substrates for the construction of cholesterol oxidase modified electrode and well realized the direct electron transfer between the enzyme and electrode. The modified gold nanoparticles could further catalyze the products of cholesterol oxidation catalyzed by cholesterol oxidase, which was beneficial to the enzyme-catalyzed reaction. The as-fabricated bioelectrode exhibited excellent electrocatalytic performance for the cholesterol with a linear range of 7.5–280.5 µmol·L −1 , a low detection limit of 2.1 µmol·L −1 , good stability and reproducibility. Moreover, the electrochemical biosensor showed good selectivity and acceptable accuracy for the detection of cholesterol in human serum samples.
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Biosensors-Basel
·
2023
·Vol. 13
·期 7
·723
·
IF 5.4
Fengli Gao,Gang Liu,Yishu Qiao,Xiuwen Dong,Lin Liu
This work reports the development of a fluorescence method for the detection of poly(ADP-ribose) polymerase-1 (PARP1), in which a phenylboronic acid-modified fluorescein isothiocyanate dye (FITC-PBA) was used to recognize the formed poly(ADP-ribose) (PAR) polymer. The detection system was designed by conjugating recombinant streptavidin (rSA) with PARP1-specific double-stranded DNA (dsDNA) through streptavidin–biotin interaction. Capture of PARP1 via rSA–biotin–dsDNA allowed for the poly-ADP-ribosylation (PARylation) of both rSA and PARP1 in a homogeneous solution. The resulting rSA–biotin–dsDNA/PAR conjugates were then captured and separated via the commercialized nitrilotriacetic acid–nickel ion-modified magnetic bead (MB-NTA-Ni) through the interaction between NTA–Ni on MB surface and oligohistidine (His6) tag in rSA. The PAR polymer could capture the dye of FITC-PBA through the borate ester interaction between the boronic acid moiety in PBA and thecis-diol group in ribose, thus causing a decrease in fluorescence signal. The PARylation of streptavidin and the influence of steric hindrance on PARylation efficiency were confirmed using reasonable detection strategies. The method showed a wide linear range (0.01~20 U) and a low detection limit (0.01 U). This work should be valuable for the development of novel biosensors for the detection of poly(ADP-ribose) polymerases and diol-containing species.Keywords:streptavidin;nitrilotriacetic acid;magnetic bead;poly(ADP-ribose) polymerase;boronic acid;immobilization-free
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Small
·
2023
·
IF 13.3
Min Hou,Rui Guo,Tianyu Ren,Tao Wang,Jian-Hui Jiang,Jianjun He
Dysfunctional transcription factors that activate abnormal expressions of specific proteins are often associated with the progression of various diseases. Despite being attractive drug targets, the lack of druggable sites has dramatically hindered their drug development. The emergence of proteolysis targeting chimeras (PROTACs) has revitalized the drug development of many conventional hard-to-drug protein targets. Here, the use of a palindromic double-strand DNA thalidomide conjugate (PASTE) to selectively bind and induce proteolysis of targeted activated transcription factor (PROTAF) is reported. The selective proteolysis of the dimerized phosphorylated receptor-regulated Smad2/3 and inhibition of the canonical Smad pathway validates PASTE-mediated PROTAF. Further aptamer-guided active delivery of PASTE and near-infrared light-triggered PROTAF are demonstrated. Great potential in using PASTE for the selective degradation of the activated transcription factor is seen, providing a powerful tool for studying signaling pathways and developing precision medicines.
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Small
·
2013
·Vol. 10
·期 5
·980-988
·
IF 7.823
Shengwang Zhou,Xuezhong Du,Fangbo Cui,Xianfeng Zhang
Novel DNA-gated mesoporous silica nanoparticle (MSN) vehicles functionalized with disulfide-linked acridinamine intercalators are constructed for multi-responsive controlled release. The DNA-gated MSN vehicles release cargo encapsulated in the MSN pores under different stimuli, including disulfide reducing agents, elevated temperature, and deoxyribonuclease I (DNase I), for codelivery of drugs and DNA/genes in different forms. Furthermore, the cascade release of encapsulated and intercalative drugs is controlled by AND logic gates in combination of dual stimuli. The ingeniously designed DNA-gated MSN vehicles integrates multiple responses and AND logic gate operations into a single smart nanodevice not only for codelivery of drugs and DNA/genes but also for cascade release of two drugs and has promising biological applications to meet diverse requirements of controlled release.
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International Journal of Nanomedicine
·
2023
·
IF 8
Chao Zhang,Mengnan Han,Fanghua Zhang,Xueli Yang,Jie Du,Honglei Zhang,Wei Li,Shengxi Chen
Background Chemotherapy, as an adjuvant treatment strategy for HER2-positive breast cancer, can effectively improve clinical symptoms and overcome the drug resistance of therapeutic monoclonal antibodies. Nucleoside analogues are a class of traditional chemotherapeutic drugs that are widely applied in adjuvant therapy. However, there are many critical issues that limit their clinical efficiency, including poor selectivity and stability, severe side effects and suboptimal therapeutic efficacy. Hence, this work aims to develop a new DNA nanocarrier for targeted drug delivery to solve the above problems.Methods Four 41-mer DNA strands were synthesized and 10 FUdR molecules were attached to 5ʹ end of each DNA strand by DNA solid-phase synthesis. An affibody molecule was connected to the end of polymeric FUdR through a linker in one of the four strands. The affibody-FUdR-tetrahedral DNA nanostructures (affi-F/TDNs) were self-assembled through four DNA strands, in which one vertex was connected to an affibody at the end of a polymeric FUdR tail and three vertices were only polymeric FUdR tails. In vitro cellular uptake of affi-F/TDNs was examined visually with confocal fluorescence microscopy and flow cytometry, and the cytotoxicity of affi-F/TDNs against cancer cells was investigated with MTT assay. Cell apoptosis was detected by Annexin V-FITC/PI double staining method. Using NOD/SCID (Mus Musculus) mice model, the targeted killing efficacy of affi-F/TDNs was also evaluated.Results The drug-loading of FUdR in affi-TDNs was 19.6% in mole ratio. The in vitro results showed that affi-F/TDNs had high selectivity and inhibition (81.2%) for breast cancer BT474 cells overexpressing HER2 and low toxicity in MCF-7 cells with low HER2 expression. During the in vivo application, affi-F/TDNs displayed good stability in the blood circulation, achieved specific accumulation in tumor region and the best antitumor efficacy (inhibition ratio of 58.1%), and showed excellent biocompatibility.Conclusions The affibody-DNA tetrahedrons, as a simple and effective active targeting delivery nanocarrier, provided a new avenue for the transport of nucleoside antitumor drugs.
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MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Qiao Xu,Ke Liu,Jingjing Jin,Xinfeng Zhang
The assay of biomarker proteins is of critical importance for disease diagnosis. In this work, we have designed a cascaded strand displacement reaction system for detection of low abundant biomarker protein in serum samples. The proposed binding-induced strand displacement conversion system, first converts a protein recognition event into the output of the DNA (cDNA) catalyst, and then the output cDNA catalytically load the reporter DNAzyme onto magnetic beads based on catalyzed hairpin assembly (CHA) reaction. The high density of the hairpin DNA on a magnetic bead surface results in an over 20-fold improvement in the reaction efficiency of CHA, compared with conventional CHA. In addition, the magnetic beads are able to efficiently separate the serum sample matrix that could remarkably affect the DNAzyme-catalyzed chemiluminescent (CL) reaction. This type of magnetic biosensor allows for the detection of 0.5 pM target protein in serum samples, whereas when using homogenous CHA biosensors, the CL signal for 2 nM PDGF-BB is seriously inhibited by the serum matrix. Since the sensing system integrates the protein recognition, signaling, signal amplification and matrix separation functions, it is promising for the assay of proteins in biological samples.
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JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Jinjin Liu,Dan Wang,Shuya Wang,Xiaojing Shi,Tingli Xiong,Yebin Lu,Jianbo Yang,Wei Wei,Xuejun Gong,Qiong Huang,Liandong Ji,Kelong Ai
Acute pancreatitis (AP), a potentially fatal disorder driven by macrophage-associated inflammation, involves mitochondrial reactive oxygen species (ROS) overproduction with pancreatic acinar cells (PACs). This ROS surge damages mitochondria, causing mitochondrial DNA (mt-DNA) leakage and PACs apoptosis. Released mt-DNA then activates the pro-inflammatory cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in macrophages, exacerbating disease progression. Critically, while scavenging mitochondrial ROS can halt this cycle, existing mitochondria-targeted drugs fail to penetrate the damaged blood-pancreas barrier (BPB). To overcome this limitation, we developed MTP, a novel dual-targeting nanomedicine synthesized from tannic acid, dopamine, and molybdenum oxides. MTP uniquely achieves dual targeting: actively homing to injured BPB and specifically accumulating within PACs mitochondria. This enables robust mitochondrial ROS scavenging, which protects mitochondrial integrity, reduces mt-DNA release, inhibits PACs apoptosis, and crucially blocks mt-DNA-induced cGAS-STING activation in macrophages, thereby suppressing their pro-inflammatory M1 polarization. By simultaneously interrupting both ROS-mediated PACs damage and macrophage-driven inflammation via this dual-targeting strategy, MTP effectively mitigates AP progression, establishing a breakthrough therapeutic approach.
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APPLIED SPECTROSCOPY
·
2023
·
IF 3.5
Ning-Ning Wu,Lin-Ge Chen,Hai-Bo Wang
A sensitive fluorescent sensor has been developed for the determination of tetracycline (TC) using adenine thymine (AT)-rich single-stranded DNA (ssDNA) templated copper nanoclusters (CuNCs) as a fluorescent probe. Fluorescent ssDNA-CuNCs were synthesized by employing AT-rich ssDNA as templates and ascorbic acid as reducing agents through a facile one-step method. The as-prepared ssDNA-CuNCs exhibited strong fluorescence with a large Stokes shift (240 nm) and stable fluorescence emission. In the presence of TC, the fluorescent intensity of ssDNA-CuNCs was obviously decreased through the inner filter effect, due to the spectral overlapping between ssDNA-CuNCs and TC. Under the optimal conditions, the strategy exhibited sensitive detection of TC with a linear range from 2 nM to 30 μM and with a limit of detection of 0.5 nM. Furthermore, the sensor was successfully applied for the detection of TC in milk samples. Therefore, it provided a simple, rapid, and label-free fluorescent method for TC detection.
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