JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yeyang Wu,Yanmei Li,Ni Yan,Jiaqi Huang,Xinyu Li,Keyan Zhang,Zhenming Lu,Ziwen Qiu,Hong Cheng
Stimulator of the interferon genes (STING) pathway is appealing but challenging to potentiate the innate anti-tumor immunity. In this work, nuclear-targeted chimeric peptide nanorods (designated as PFPD) are constructed to amplify innate immunity through localized DNA damage and STING activation. Among which, the chimeric peptide (PpIX-FFVLKPKKKRKV) is fabricated with photosensitizer and nucleus targeting peptide sequence, which can self-assemble into nanorods and load STING agonist of DMXAA. The uniform nanosize distribution and good stability of PFPD improve the sequential targeting delivery of drugs towards tumor cells and nuclei. Under light irradiation, PFPD produce a large amount of reactive oxygen species (ROS) to destroy nuclear DNA in situ , and the released cytosolic DNA fragment will efficiently activate innate anti-tumor immunity in combination with STING agonist. In vitro and in vivo results indicate the superior ability of PFPD to activate natural killer cells and T cells, thus efficiently eradicating lung metastatic tumor without inducing unwanted side effects. This work provides a sophisticated strategy for localized activation of innate immunity for systemic tumor treatment, which may inspire the rational design of nanomedicine for tumor precision therapy.
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高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Bin Guo,Xiaofei Sun,Shan Tao,Tian Tian,Haozhi Lei
As medical advancements turn most cancers into manageable chronic diseases, new challenges arise in cancer recurrence monitoring. Detecting circulating tumor cells (CTCs) is crucial for monitoring cancer recurrence, but the current methods are cumbersome and costly. This study developed a new CTC detection system combining DNA aptamer recognition, hybridization chain reaction (HCR) technology, and DNA logic devices, enabling the one-step recognition of CTCs by identifying multiple membrane proteins. After catalytically active Au nanoparticles were attached through reduction synthesis in situ onto the DNA hybridization strands of the CTCs surface, a 3,3′,5,5′-tetramethylbenzidine (TMB) colorimetric reaction was used to detect CTCs concentration via peroxidase-like catalysis. With this CTCs detection reporting system, we achieved an LOD of 4 cells/mL using an ultraviolet–visible (UV–vis) spectrophotometer. At certain concentrations, CTCs could even be detected visually without the need for an instrument. The development of this CTCs detection reporting system provided a convenient, reliable, and cost-effective detection strategy for widespread CTCs-based cancer recurrence monitoring.
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高影响因子
ACS Nano
·
2024
·
IF 15.8
Weijun Wang,Wenqing Wang,Yaxin Chen,Mengling Lin,Yan-Ru Chen,Ruijin Zeng,Tenghang He,Zhifa Shen,Zai-Sheng Wu
A major impediment to the clinical translation of DNA tiling nanostructures is a technical bottleneck for the programmable assembly of DNA architectures with well-defined local geometry due to the inability to achieve both sufficient structural rigidity and a large framework. In this work, a Y-backbone was inserted into each face to construct a superlarge, sufficiently rigidified tetrahedral DNA nanostructure (called RDT) with extremely high efficiency. In RDT, the spatial size increased by 6.86-fold, and the structural rigidity was enhanced at least 4-fold, contributing to an ∼350-fold improvement in the resistance to nucleolytic degradation even without a protective coating. RDT can be mounted onto an artificial lipid-bilayer membrane with molecular-level precision and well-defined spatial orientation that can be validated using the fluorescence resonance energy transfer (FRET) assay. The spatial orientation of Y-shaped backbone-rigidified RDT is unachievable for conventional DNA polyhedrons and ensures a high level of precision in the geometric positioning of diverse biomolecules with an approximately homogeneous environment. In tests of RDT, surface-confined horseradish peroxidase (HRP) exhibited nearly 100% catalytic activity and targeting aptamer-immobilized gold nanoparticles showed 5.3-fold enhanced cellular internalization. Significantly, RDT exhibited a 27.5-fold enhanced structural stability in a bodily environment and did not induce detectable systemic toxicity.
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高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Shixin Cai,Ke Shi,Aohua Ji,Yilin Long,Xiaoli Wang,Yuting Zhang,Nandi Zhou
Methylation level of circulating tumor DNA (ctDNA) is widely recognized as a pivotal biomarker in precision oncology for tumor characterization and risk assessment. However, current point-of-care testing platforms for methylation analysis are constrained in achieving sufficient detection specificity due to their limitations in single-locus detection and their dependence on complex instrumentation. In this study, to overcome the above limitations, a smartphone-integrated, microfluidic chip technology-based biosensing platform was engineered for simultaneous analysis of multiple methylation loci in ctDNA. In this platform, whole blood samples from suspected individuals underwent GlaI methylation-sensitive enzyme digestion and target-specific primer hybridization, followed by microfluidic chip loading for on-chip colorimetric reactions. Methylation levels at specific loci were quantified through chamber-specific absorbance measurements by using the developed portable biosensing platform. The biosensor achieved simultaneous detection of three specific methylation loci (CpG sites) on the Septin 9 gene, which are associated with colorectal cancer. The detection limits (LODs) for the individual methylation loci are 0.25, 0.4, and 0.525 fM, respectively. This platform demonstrates high accuracy in detecting methylation signatures within blood samples from colorectal cancer patients, showing a significant correlation with conventional diagnostic methods. With its low cost and portable features, the developed biosensing platform may provide an economical solution for early-stage screening of cancer for the healthcare system in remote and under-resourced regions.
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NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Lu Sun,Qian-Yue Xu,Hai-Bo Wang
In order to meet the demand of analyzing low concentrations of DNA with high sensitivity, herein, a magnetic separated-type fluorescent biosensor has been constructed for ultrasensitive DNA assay based on chemically driven redox-cycling system. In this study, the substrate o-phenylenediamine dihydrochlorlde (OPD) could be oxidized to produce 2, 3-diaminophenazine (DAP) with strong fluorescence emission at 555 nm. In the chemically driven redox-cycling system, Cu2+ oxidized OPD to yield DAP and Cu+/Cu0. On one hand, the produced Cu0 could further oxidize OPD to form DAP. But on the other, the generated Cu+ could react with newly imported H2O2 to undergo a Fenton-like reaction to form hydroxyl radicals (•OH) and Cu2+ ion. The reproduced Cu2+ ion and generated •OH could in turn oxidize OPD to form more DAP, which touching off a chemically driven chemical redox-cycling amplification reaction. By leveraging of the magnetic separation-mode, the chemically driven redox-cycling strategy allowed quantitative detection of H1N1, exhibiting a linear ranging from 1 pM to 1 nM with a low limit of detection of 300 fM. The magnetic separation-mode could effectively minimize the background signal to obtain greatly improved sensitivity. It’s promising that the chemically driven redox-cycling strategy would provide a novel way in the fields of biosensing and biological samples assay.
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ACS Sensors
·
2025
·
IF 9.1
Mengqi Huang,Kunte Shang,Luyi Ying,Yuqi Han,Ningxi Hong,Yu-Feng Yao
Rapid and precise detection of specific DNA is valuable for biological research and clinical disease diagnosis. Clustered regularly interspaced short palindromic repeat (CRISPR) technology can enhance existing DNA testing, making DNA detection faster, more portable, and more accurate. This study presents a new Cas12-driven exponential amplification-based lateral flow biosensor (CADEX-LF) for rapid and highly sensitive DNA detection. CADEX-LF takes full advantage of the highly specific target-loading-dependent trans-cleavage activity of Cas12 and the extremely high efficiency of nicking endonuclease-mediated exponential amplification. The adoption of lateral flow readout enables CADEX-LF for point-of-care (POC) use without requiring complicated supplementary equipment. CADEX-LF was shown to achieve a detection sensitivity of 2 × 10–15 M within 45 min of measurement time and displayed outstanding specificity with double-base resolution. Furthermore, CADEX-LF could identify herpes simplex virus 1 (HSV-1) DNA in tears of rabbits and clinical patients with HSV-1 keratitis, exhibiting its practical application potential in clinical diagnosis. The proposed CADEX-LF biosensor may have great promise for point-of-care disease diagnosis in resource-limited environments.
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高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Kaiping Sun,Xiaoyi Yan,Luo Li,Yunxue Zhu,Puyu Zhao,Zhiquan Zhang
Mercury pollution has always been a concern due to its high toxicity and persistence. In this study, we designed an aptamer-based sensor relying on lanthanide metal-organic framework and in-situ generation of active substances through electrochemical conversion. Firstly, a lanthanide metal-organic framework with rod-shaped structure was successfully synthesized, which has higher conductivity and stability compared to traditional MOFs. By possessing the substantial specific surface area and profusion of active sites offered by rod-shaped Gd 4 -MOF, gold nanoparticles (AuNPs) were deposited for the connection of tetrahedron DNA nanostructure (TDN). The active substances generated by electrochemical conversion has a more stringent arrangement and better response current compared to ordinary active substances, which can be used for ultra trace detection of mercury with higher sensitivity. After mercury added, DNA and mercury specifically bind to form thymine–Hg–thymine (T-Hg-T) structures, which cause changes in response current through conformational changes. The results demonstrated that a pronounced linear correlation between the DPV response and mercury concentration was observable, with a linear range of 1 fM to 200 fM and a detection limit of 0.66 fM. This sensor is successfully applied to detect the mercury content in marine products, so it has great application prospects for preventing and controlling mercury pollution.
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Advanced Healthcare Materials
·
2024
·
IF 10
Yijing Zhang,Xisen Cao,Guang Hu,Rui Ye,Li Zhang,Jie Song
Interleukin-12 (IL-12) is a critical cytokine with notable anticancer properties, including enhancing T-cell-mediated cancer cell killing, and curbing tumor angiogenesis. To date, many approaches are evaluated to achieve in situ overexpression of IL-12, minimizing leakage and the ensuing toxicity. Here, it is focused on circular single-stranded DNA (Css DNA), a type of DNA characterized by its unique structure, which could be expressed in mammals. It is discovered that Css DNA can induce sustained luciferase expression for half a year by intramuscular injection and showed effective antitumor results by intratumoral injection. Motivated by these findings, a folate-modified LNP system is now developed for the delivery of Css DNA expressing IL-12 for the therapy of 4T1 triple-negative breast cancer (TNBC). This delivery system effectively activates anti-cancer immune responses, slows tumor growth, significantly prolongs survival in animal models, and prevents tumor recurrence. After 6 months of long-term observation, the elevated level of IL-12 is still detectable in the lymph nodes and serum of the cured mice. This study highlights the long-term sustained expression capacity of Css DNA and its ability to inhibit recurrence, and the potential of tumor-targeted LNPs for Css DNA-based cancer therapy, providing a new insight into gene overexpression strategy.
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高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
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.
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Bioactive Materials
·
2023
·
IF 18.9
Hongyan Wei,Fenfang Li,Tiantian Xue,Haixia Wang,Enguo Ju,Mingqiang Li,Yu Tao
As the most abundant liver-specific microRNA, microRNA-122 (miR122) played a crucial role in the differentiation of stem cells into hepatocytes. However, highly efficient miR122 delivery still confronts challenges including poor cellular uptake and easy biodegradation. Herein, we for the first time demonstrated that the tetrahedral DNA (TDN) nanoplatform had great potential in inducing the differentiation of human mesenchymal stem cells (hMSCs) into functional hepatocyte-like cells (HLCs) by transferring the liver-specific miR122 to hMSCs efficiently without any extrinsic factors. As compared with miR122, miR122-functionalized TDN (TDN-miR122) could significantly up-regulate the protein expression levels of mature hepatocyte markers and hepatocyte-specific marker genes in hMSCs, indicating that TDN-miR122 could particularly activate the hepatocyte-specific properties of hMSCs for developing cell-based therapies in vitro . The transcriptomic analysis further indicated the potential mechanism that TDN-miR122 assisted hMSCs differentiated into functional HLCs. The TDN-miR122-hMSCs exhibited hepatic cell morphology phenotype, significantly up-regulated specific hepatocyte genes and hepatic biofunctions in comparison with the undifferentiated MSCs. Preclinical in vivo transplantation appeared that TDN-miR122-hMSCs in combination with or without TDN could efficiently rescue acute liver failure injury through hepatocyte function supplement, anti-apoptosis, cellular proliferation promotion, and anti-inflammatory. Collectively, our findings may provide a new and facile approach for hepatic differentiation of hMSCs for acute liver failure therapy. Further large animal model explorations are needed to study their potential in clinical translation in the future.
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高影响因子
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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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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