MICROCHIMICA ACTA
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2023
·Vol. 190
·期 4
·1-9
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IF 5.7
Su Zhanying,Zhang Li,Yu Ying,Lin Bixia,Wang Yumin,Guo Manli,Cao Yujuan
An electrochemical strategy based on bimetallic nanozyme in collaboration with toehold-mediated DNA replacement effect is proposed for the sensitive determination of miRNA-21. The AuPt nanoparticles (AuPt NPs) are prepared as a catalytic beacon; it shows favorable peroxidase properties with a Michaelis contant ( K m ) of 0.072 mM for H 2 O 2 , which is capable of catalyzing H 2 O 2 to induce an intense redox reaction, and causing a measurable electrochemical signal. To further enhance the strength of the signal response, a novel toehold-mediated DNA replacement strategy is employed. DNA strands with specific sequences are modified on electrodes and AuPt NPs, respectively. In the presence of miRNA-21, a cyclic substitution effect is subsequently activated via a specific toehold sequence and leads to a large accumulation of AuPt NPs on the electrodes. Subsequently, a strong signal depending on the amount of miRNA-21 is obtained after adding a small amount of H 2 O 2 . The analytical range of this determination method is from 0.1 pM to 1.0 nM, and the LOD is 84.1 fM. The spike recoveries for serum samples are 95.0 to 102.4% and the RSD values are 3.7 to 5.8%. The results suggests a promising application of the established method in clinical testing and disease diagnosis. Graphical Abstract
研究领域:
生物化学
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分子诊断
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纳米医学
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2023
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IF 8.4
Weihua Zhao,Jun Xu,Hongbo Li,Shengliang Zhong,Ruqin Yu
MiRNA can exist in body fluids and its changes directly affect human life and health, which has been a research hotspot in recent years. In this work, we designed an enzyme-free sensing system for highly sensitive detection of miRNA-21 based on strand displacement reaction (SDR) that can recycle the target and functional hairpin probes (HP) that modified on upconversion nanomaterials (UCNPs). The target gene circulates through the SDR process and completes the initial signal amplification process. Then, the C2 sequences and targets released by the SDR process can continue to be combined with functional hairpin probes modified with fluorophore and quenching groups. After infrared irradiation, HP is broken, and C2 or the target can take the fluorophores away from the quenching group, so that the fluorescence signal can be detected to achieve highly sensitive detection of the target. In sensing system, the use of magnetic beads can reduce the background signal during the reaction process, and the functional hairpin probe can accurately turn the signal on and off. The sensor system not only shows excellent detection performance (detection limit of 30.3 fM) in buffer and actual detection, but also has excellent selectivity, which can provide a new detection method for miRNA-21 detection.
研究领域:
生物化学
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分子生物学
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纳米医学
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高影响因子
BIOELECTROCHEMISTRY
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2024
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IF 4.8
Tang-Bin Liao,Ke-Xin Luo,Ji-Yuan Tu,Yu-Lin Zhang,Guo-Jun Zhang,Zhong-Yue Sun
MiRNA-21 is recognized as an important biological marker for the diagnosis, treatment, and prognosis of breast cancer. Here, we have created a nanochannel biosensor utilizing the duplex-specific nuclease (DSN) signal amplification strategy to achieve the detection of miRNAs. In this system, DNA as the capture probe was covalently immobilized on the surface of nanochannels, which hybridized with the target miRNA and forms RNA/DNA duplexes. DSN could cleave the probe DNA in RNA/DNA duplexes, recycling target miRNA, which may again hybridized with other DNA probes. After N cycles, most of the DNA probes had been cleaved, and the content of miRNA could be quantified by detecting changes in surface charge density. This biosensor can distinguish miR-21 from non-complementary miRNAs and one-base mismatched miRNAs, with reliable detection limits as low as 1 fM in PBS. In addition, we had successfully applied this method to analysis of total RNA samples in MCF-7 cells and HeLa cells, and the nanochannels had also shown excellent responsiveness and strong anti-interference ability. This new method is expected to contribute to miRNA detection in clinical diagnostics, providing a unique approach to detecting and distinguishing disease-associated molecules.
研究领域:
分子生物学
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医学诊断
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纳米技术
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PubMed
高影响因子
Small
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2026
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IF 11.8
Qian Guo,Junyang Chen,Yu-Lu Wang,Qi-Yan Lv,Xiao-Qing Ling,Xiaojie Song,Hui-Fang Cui
Downregulating oncogenic microRNAs (miRNAs) is an attractive strategy for reversing drug resistance in cancer therapy. Compared to antisense, DNAzyme (Dz) possesses advantages such as recyclability and stability. However, it still suffers from insufficient stability and inadequate endogenous cofactors. Herein, by using miRNA-21 (miR-21) as target, MCF-7/ADR as tumor model, a multi-modality, polyvalent, Spherical Nucleic Acids (SNAs)-type drug delivery system (DDS) was developed. A Y-DNA nanoassembly was synthesized, and directional immobilized on polydopamine@MnO 2 (PDM) nanoparticles. The Y-DNA contains two Dz sequences for cleaving miR-21, and a tumor-targeting aptamer. Doxorubicin was loaded at a loading rate of 23.33%. The DDS dramatically improved the Dz stability, self-supplied cofactors, efficiently targeted tumor tissues and cells. Additionally, it relieved hypoxia, depleted glutathione, generated reaction oxygen species, and transferred near-infrared light to heat. Consequently, highly responsive, and DNase resistant cleavage of miR-21 was realized. Intracellular miR-21 was efficiently downregulated. Doxorubicin was controllably and efficiently released. With the PDM@Y-DNA@D (Laser+) treatment, the cancer cell viability lowered to ≤3%, and tumor growth inhibition reached to 86%. Molecular mechanisms involved in the drug resistance reversal were investigated. The DDS provides a promisingly transformable therapeutic platform for drug resistant cancers, and for targeting other and multiple oncogenic miRNAs.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2026
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IF 9.6
Cannan Zhao,Shuai Wen,Yusheng Feng,Yingying Xiong,Qiuyue Liu,Qiusha Li,Jinglei Xu,Wei Wang,Jian Wang
MicroRNAs (miRNAs) serve as critical biomarkers for early cancer diagnosis due to their disease-specific expression profiles, yet their low abundance and complex matrix interference pose significant challenges for conventional detection methods. To address these limitations, an innovative chiral biosensing platform that synergistically integrates helical gold nanorods (HGNRs) with hybridization chain reaction (HCR) amplification and magnetic beads (MBs)-assisted separation for highly sensitive and specific detection of miRNA-21 is developed. In this proposed method, target miRNA-21 initiates cDNA displacement on MB surfaces, triggering HCR to generate extended DNA polymers with multiple streptavidin-alkaline phosphatase (SA-ALP) conjugation sites. Subsequent ALP-mediated conversion of ascorbic acid 2-phosphate (AAP) to ascorbic acid induces structural change of HGNRs, leading to detectable circular dichroism (CD) signal reduction. This integrated approach demonstrates remarkable sensitivity as low as 3.025 pmol/L, and excellent selectivity with successful validation in diluted human serum matrices. The chiral CD transduction strategy pioneers a new paradigm for miRNA analysis by synergizing chiral nanomaterial and enhanced signal transduction with cascade amplification, offering significant potential for clinical liquid biopsy applications.
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高影响因子
Advanced Science
·
2022
·Vol. 10
·期 4
·2205886
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IF 17.521
Minghua Deng,Zhanpeng Ren,Huibin Zhang,Ziqin Li,Chenglong Xue,Jianying Wang,Dan Zhang,Huan Yang,Xianbao Wang,Jinhua Li
The incidence of prostate cancer (PCa) in men globally increases as the standard of living improves. Blood serum biomarker prostate-specific antigen (PSA) detection is the gold standard assay that do not meet the requirements of early detection. Herein, a solution-gated graphene transistor (SGGT) biosensor for the ultrasensitive and rapid quantification detection of the early prostate cancer-relevant biomarker, miRNA-21 is reported. The designed single-stranded DNA (ssDNA) probes immobilized on the Au gate can hybridize effectively with the miRNA-21 molecules targets and induce the Dirac voltage shifts of SGGT transfer curves. The limit of detection (LOD) of the sensor can reach 10 −20 M without amplification and any chemical or biological labeling. The detection linear range is from 10 −20 to 10 −12 M. The sensor can realize real-time detection of the miRNA-21 molecules in less than 5 min and can well distinguish one-mismatched miRNA-21 molecule. The blood serum samples from the patients without RNA extraction and amplification are measured. The results demonstrated that the biosensor can well distinguish the cancer patients from the control group and has higher sensitivity (100%) than PSA detection (58.3%). Contrastingly, it can be found that the PSA level is not directly related to PCa.
研究领域:
生物医学工程
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分子诊断学
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纳米技术
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PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2025
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IF 10.5
Shixin Cai,Rongfeng Cai,Sanxia Wang,Xin Chen,Lele Zhang,Yunpeng Zhao,Xiaoli Wang,Yuting Zhang,Nandi Zhou
Circulating tumor cells (CTCs) are closely associated with cancer progression and metastasis, making the development of precise CTCs enumeration technology crucial for real-time cancer monitoring and post-operative treatment. Researches indicated that miRNA-21 exhibits abnormally high expression in CTCs and can thus serve as a biomarker for CTCs profiling. Herein, an innovative dual-responsive detection platform was developed by integrating miRNA-21/pH-activated ZnO@Au NPs-hairpin DNA (HP) nanoprobes with microfluidic single-cell droplet technology for CTCs identification. In this platform, ZnO@Au NPs-HP nanoprobes and CTCs are co-encapsulated into single-cell droplets, after which the nanoprobes enter CTCs. Leveraging the characteristic intracellular high miRNA-21 level and acidic microenvironment of CTCs, Zn-DNAzyme contained in HP can be activated to cleave its substrate chain and the fluorescence is thus restored. This strategy effectively avoids the interference from free miRNA-21 in blood and enhances detection specificity. Subsequent droplet fluorescence detection enables the accurate CTCs quantification. The platform enables robust detection and precise isolation of CTCs in blood samples from three distinct cancer cell types HCT116, HepG2 and HeLa, and achieves remarkably high sensitivity with successful recovery of 5 CTCs/mL in spiked human blood samples. Furthermore, the platform has been successfully applied for the accurate counting of CTCs in whole blood samples from patients with three types of cancers, i.e. colorectal cancer, hepatocellular carcinoma, and cervical cancer. Therefore, the established system exhibits superior detection performance and significant clinical potential, providing a robust tool for liquid biopsy and personalized cancer management.
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高影响因子
COMPOSITES PART B-ENGINEERING
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2022
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IF 11.322
Yu Wang,Mingyan Deng,Ye Wu,Cheng Hu,Bo Zhang,Chuan Guo,Haoyang Song,Qingquan Kong,Yunbing Wang
The progression of intervertebral disc degeneration (IDD) is characterized by an initial chronic local inflammatory response and ultimately leads to unbalanced anabolic/catabolic activity within the nucleus pulposus (NP). Injectable inflammation-responsive hydrogels have great potential in treating IDD through on-demand local drug delivery. Here, we designed an injectable inflammation-responsive gelatin-based hydrogel for local and sustained delivery of the naturally extracted anti-inflammatory curcumin and a cholesterol-modified miRNA-21 inhibitor (Antagomir-21) to treat IDD. We successfully demonstrated the robust biocompatibility and ideal inflammation-responsive and on-demand drug release properties of hydrogels, as well as the great potential of IDD regeneration. This work proposes the novel inflammation-responsive hydrogel-based curcumin and miRNA delivery systems for the treatment of IDD.
研究领域:
生物医学工程
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药学
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再生医学
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Qi Wang,Wenyong Li,Juan Xia,Hai Wu,Lijun Wu,Jianguo Xu
The construction of DNA nanodevices is vital for disease diagnosis and biomedical study. Herein, we proposed a ternary DNA nanomachine for microRNA determination using a molecular beacon (MB) coupled Y shape probe (MB-YP). The MB-YP was a tripartite junction scaffold connected with MB-Y I , Y II , and Y III . The target miRNA firstly recognizes MB-Y I , activating the MB-Y I -DNA nanomachine to produce endogenous primer I (EP I ) responsible for the activation of Y II -DNA nanomachine. The Y II -DNA nanomachine then allows the production of numerous EP II , which in turn activates the Y III -DNA nanomachine to produce EP III for re-activating MB-Y I -DNA nanomachine. The stepwise operated MB-Y I -DNA nanomachine, Y II -DNA nanomachine, and Y III -DNA nanomachine constituted the ternary DNA nanomachine and the repeated use of EP I , EP II , and EP III permits it an all-in amplification. These features lead to the opening of MB-Y I for emitting strong fluorescence. As low as 1 fM miRNA can thus be quantitatively detected and the linear response of the miRNA is from 1 fM to 100 pM (six orders of magnitude). Moreover, the nanomachine is specific to distinguish target miRNA from one-base mutant, inserted, and deleted target analogs. Its practicability was demonstrated by confirming miRNA-21 is overexpressed in clinical human serums from lung cancer patients than healthy donors.
研究领域:
生物医学工程
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分子生物学
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纳米技术
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癌症诊断
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高影响因子
ANALYTICA CHIMICA ACTA
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2025
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IF 6
Jiale Wang,Minghua Deng,Chuanquan Wang,Kunpeng Niu,Ning Wang,Jinhua Li,Binyun Xia,Liyun Ding,Huan Yang,Xiaohan Chen,Jiayi Zhu
Background Efficient and rapid identification of trace amounts of microRNA-21 (miRNA-21), an oncogenic miRNA, is conducive to the early diagnosis of prostate cancer. Despite extensive research efforts, the development of biosensors capable of achieving clinically relevant sensitivity and limits of detection (LOD) remains challenging, primarily due to the ultralow physiological concentrations of cancer biomarkers in human biological systems. Beyond that, the suboptimal probe designs such as complex sensing structures and unstable sensing materials collectively lead to inadequate repeatability and stability for clinical application. Results Hence, in this work, a label-free and highly sensitive optical fiber Surface Plasmon Resonance (SPR) biosensor with ultralow LOD was developed for detecting miRNA-21, which was fabricated simply by coating a layer of Au film and gold nanoparticles (AuNPs) onto a multimode-single-mode-multimode (MSM) optical fiber, and then biofunctionalized with optimized single-stranded DNA (ssDNA) enabling the quantification of miRNA-21. Excitingly, the biosensors, which have a simple composition and demonstrated with excellent linearity, specificity and stability, were experimentally verified to reach an ultra-low LOD of 1.86 × 10 –19 M that significantly lower than current detection method and high sensitivity of 3021.48 RIU/nm. And detection of trace miRNA-21 was enabled without RNA amplification. The sensor's capability to effectively differentiate prostate cancer patients from healthy controls was demonstrated by testing clinical serum samples and the sensor achieved higher detection accuracy compared to the commonly used clinical prostate-specific antigen (PSA) quantification. Significance The proposed sensing platform processes the merits of simple configuration as well as low cost and has potential to auxiliary early-stage diagnosis of various cancers by detecting associated biomarkers.
研究领域:
生物医学工程
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生物传感器
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肿瘤学
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纳米技术
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即时检测
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2026
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IF 5.2
Lulu Dong,Jianhua Wang,Haiqin Li,Yinrong Yang,Xiaochun Li
A low-background paper platform enables cascaded RCA-based ratiometric sensing. • Blue CQDs provide self-calibrated and reliable miRNA-21 quantification. • Smartphone-assisted portable POCT enables noninvasive urinary miRNA analysis. The non-invasive detection of microRNA-21 (miRNA-21), a promising biomarker for bladder cancer, is challenged by its low abundance in urine and the lack of portable, sensitive analytical methods. Herein, we report an integrated smartphone-based paper microfluidic platform that combines rolling circle amplification (RCA), DMSN-based fluorescence enhancement, carbon quantum dots (CQD) -assisted ratiometric fluorescence detection, and smartphone imaging into a portable analytical system for quantitative miRNA-21 detection. A ratiometric fluorescence strategy is employed using blue-emitting CQDs covalently immobilized on glass fiber filter paper as an internal reference, while the RCA product is detected by a DMSN-coated QD probe. Under optimal conditions, the method achieves a limit of detection (LOD) of 1.06 nM for miRNA-21 with a linear range of 0.25–200 nM (R 2 = 0.9891). The assay exhibits excellent specificity against mismatched sequences and other miRNAs, and spike-recovery tests in artificial urine yield recoveries of 88.5–120.3% with relative standard deviations below 15%. The platform shows good batch-to-batch reproducibility (RSD < 7%). Spike recovery tests using clinical urine samples from healthy individuals yielded recoveries of 86.97%–108.5%, confirming the method's high accuracy and reliability in complex urine matrices. Integrated with a 3D-printed portable device and a custom smartphone application, this paper-based sensing platform provides a practical, low-cost, and portable analytical platform for point-of-care testing (POCT) of miRNA-21. The graphical abstract was prepared using SolidWorks, Cinema 4D (C4D), and Microsoft PowerPoint. No AI-assisted tools were used in the generation, preparation, or editing of the figures or graphical abstract. Download: Download high-res image (158KB) Download: Download full-size image
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高影响因子
International Journal of Nanomedicine
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2026
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IF 8.7
Jian Tao,Binbin Zeng,Caili Bi,Minyi Xu,Xiaxian Gu,Dingding Jing,Jun Sun
Purpose Ultra-sensitive detection of exosomal miR-21 is crucial for the early diagnosis of colorectal cancer. This study aims to develop a cascade amplification platform based on surface-enhanced Raman scattering (SERS), combining rolling circle amplification (RCA) and CRISPR/Cas12a, to enable ultra-sensitive quantitative detection of exosomal miR-21.Methods A SERS substrate was constructed using streptavidin-modified concave gold nanocubes (CGNs), and gold double-stranded probes loaded with Raman reporter molecules were used as SERS probes. The two components are controllably linked via a single-stranded DNA molecule with a thiol group at one end and biotin at the other, forming a stable detection system. Target-triggered RCA generates a repeat sequence, which, under the mediation of crRNA, activates Cas12a cleavage, causing the probe to be released from the substrate surface and resulting in a significant attenuation of the SERS signal.Results This platform achieves three-stage cascading signal amplification via RCA, CRISPR/Cas12a, and SERS, with a detection limit at the femto-mole (fM) level and a total detection time of approximately 80 minutes. The results were consistent with those of qRT-PCR, demonstrating high sensitivity, high specificity, and reliability.Conclusion This study proposes an RCA-CRISPR-SERS cascade amplification platform that provides a highly sensitive and specific method for detecting miR-21 in exosomes, offering potential clinical value for the early diagnosis and dynamic monitoring of colorectal cancer.
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高影响因子
危险品化学品经营许可证（带存储）