MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 6
·1-13
·
IF 5.3
You Yuanqi,Ren Yu,Li Yujun,Xu Jianguo,Li Zhi,Song Shuai,Xia Jinxing,Shen Chenlin,Wang Jie
The rapid and precise monitoring of peripheral blood miRNA levels holds paramount importance for disease diagnosis and treatment monitoring. In this study, we propose an innovative research strategy that combines the catalytic hairpin assembly reaction with SERS signal congregation and enhancement. This combination can significantly enhance the stability of SERS detection, enabling stable and efficient detection of miRNA. Specifically, our paper-based SERS detection platform incorporates a streptavidin-modified substrate, biotin-labeled catalytic hairpin assembly reaction probes, 4-ATP, and primer-co-modified gold nanoparticles. In the presence of miRNA, the 4-ATP and primer-co-modified gold nanoparticles can specifically recognize the miRNA and interact with the biotin-labeled CHA probes to initiate an interfacial catalytic hairpin assembly reaction. This enzyme-free high-efficiency catalytic process can accumulate a large amount of biotin on the gold nanoparticles, which then bind to the streptavidin on the substrate with the assistance of the driving liquid, forming red gold nanoparticle stripes. These provide a multitude of hotspots for SERS, enabling enhanced signal detection. This innovative design achieves a low detection limit of 3.47 fM while maintaining excellent stability and repeatability. This conceptually innovative detection platform offers new technological possibilities and solutions for clinical miRNA detection. Graphical abstract
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Shijin Zhou,Zhidan Tian,Qinyuan Xu,Jinming Kong,Xueji Zhang
Orthogonal dual-stage ROMP cascade enables ultrasensitive miRNA-21 detection. • Scaffold construction and signal amplification are decoupled. • The sensor detects miRNA-21 with a detection limit of 2.24 aM. • High selectivity and reliable performance in complex serum matrices. Traditional ring-opening metathesis polymerization (ROMP)-based biosensors typically couple scaffold construction and signal amplification within a single polymerization step, which limits the independent optimization of mechanical stability and electrochemical performance. This study developed an orthogonal two-stage ROMP cascade amplification strategy that successfully decoupled these two processes. Target-specific hybridization first triggers Zr 4+ coordination, initiating surface-mediated metal-catalyzed ROMP to construct a dense polynorbornene scaffold bearing cyclic anhydride side chains. Subsequently, metal-free ROMP driven by visible light grafts high-density ferrocene monomers onto the pre-assembled scaffold, forming electroactive bottlebrush polymers. This biosensor achieves a detection limit for miRNA-21 as low as 2.24 aM, with a linear range from 10 aM to 1 nM, and exhibits excellent selectivity against mismatched RNA sequences, as well as reliable detection performance in complex serum matrices. The orthogonal cascade strategy proposed in this study provides a modular and versatile new platform for the ultrasensitive detection of low-abundance biomarkers. Download: Download high-res image (116KB) Download: Download full-size image
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ANALYTICAL CHEMISTRY
·
2026
·Vol. 98
·期 34
·25133-25145
·
IF 7.3
Song Zhen,Wang Yi-Hui,Wang Jing-Yi,Lin Yue,Chen Jin-Long,Wang Huai-Song
MicroRNA
(miRNA) assays often rely on solid–liquid
interfaces
for enrichment and signal transduction, but programmable regulation
of interfacial adsorption, recognition, and release remains largely
unexplored. Here, we propose an electric double layer (EDL)-programmable
nucleic-acid interfacial switch on metal–organic framework
(MOF) interfaces. In this system, EDL-mediated interfacial stabilization,
andcoordination anchoring at coordinatively unsaturated metal sites
retain probes and posthybridization duplexes within a near-surface
quenching region, producing a stable signal-off state. Increasing
ionic strength and introducing competitive polyphosphate anions (PPi/STPP)
weaken interfacial anchoring and trigger release of the complexes
into the surrounding solution, thereby generating a signal-on response.
Based on this mechanism, we developed two complementary miRNA assays:
a MIL-101(Cr)-based multiplex fluorescence platform with quencher
strands to suppress background, and a Zn 2 Ph 2 Da-enabled duplex-release strategy that generates DNA templates for
extraction-free, reverse-transcription-free one-step qPCR with a detection
limit of 10 –18 M. Both readouts discriminated liver
cancer patients from healthy controls in plasma, demonstrating the
potential of EDL-programmable interfacial chemistry for miRNA analysis.
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BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Jixuan Han,Xiaoran Liu,Ying Yan,Jingwen Ge,Han Zhao,Chen Wang,Guohong Song,Ling Zhu,Yanlian Yang
Extracellular vesicle miRNAs (EV-miRNAs) are strongly linked to cancer progression, metastasis, and drug resistance, making them promising biomarkers for precision diagnosis. However, the clinical potential of EV-miRNA-based liquid biopsies is hindered by the low abundance of EV-miRNAs and the tedious detection procedure including EV separation, purification and miRNA quantification. Here, we develop a novel one-step catalytic hairpin assembly (CHA)-based fluorescent assay for sensitive detection of EV-miRNAs assisted with DNA-mediated membrane fusion (DMF) and DNA tetrahedron (DT) (DMF-DT-CHA). This DMF-DT-CHA assay facilitates the membrane fusion between liposome and EV through interactions between DNAs for DT-CHA probe delivery into EVs, and followed by DT-CHA, which recognizes target miRNAs to initiate non-enzymatic signal amplification via CHA-based fluorescence emission. We analyzed EVs from three breast cancer cell sources using DMF-DT-CHA and the results were consistent with qPCR and the platform achieved the limit of detection (LoD) of 0.24 fM for EV-miRNAs. We performed a clinical evaluation of the DMF-DT-CHA assay platform. Recipient operating characteristic curves (ROCs) showed that the DMF-DT-CHA platform was an excellent classifier for distinguishing breast cancer (BC) patients from healthy donors and breast cancer patients from benign breast nodule patients, with area under the curve (AUC) values of 0.850 and 0.835, respectively, as well as an accuracy of 81.1% in response to treatment for triple-negative breast cancer. DMF-CT-CHA assay platform has clinical potential for cancer diagnosis and treatment monitoring.
研究领域:
生物化学
·
分子生物学
·
临床医学
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International Journal of Nanomedicine
·
2025
·
IF 6.5
Maopu Tu,Xiaoyu Deng,Bin Lai,Jiao Liu,Yingzhou Tao,Shaohua Xu,Xiaodong Li,Xiaoqiang Niu,Zhixin Li,Jiahui Huang,Jiaxin Li,Shengxun Mao,Xi Ouyang,Jiaqing Cao
Background Chemodynamic therapy (CDT) is a promising antitumor strategy that damages tumor cells by generating reactive oxygen species (ROS) to induce oxidative stress. However, antioxidant mechanisms in tumor cells greatly reduce CDT efficacy.Methods We propose using MOF-199 nanoparticles (NPs) with tumor microenvironment responsiveness as a carrier for miR-4521 to construct miR-4521@MOF-199 for cancer treatment. Polyacrylamide gel electrophoresis evaluated MOF-199’s loading and protective capacity for miR-4521. In vitro and in vivo experiments assessed the system’s antitumor effect and biosafety, with mechanisms explored.Results The miR-4521@MOF-199 NPs effectively protected and delivered miR-4521 to tumor cells. Within high-glutathione (GSH) tumor microenvironments, NP degradation released both miR-4521 and Cu2+. The increased intracellular Cu2+ triggered tumor cell apoptosis via ROS-mediated CDT while activating cuproptosis through proteotoxic stress. Concurrently, miR-4521 disrupts the oxidative stress defense mechanisms of tumor cells by inhibiting FOXM1 expression, thereby enhancing the efficacy of CDT. Furthermore, the silencing of FOXM1 can further impede tumor progression through gene regulatory mechanisms. Experimental results demonstrate that miR-4521@MOF-199 exhibits potent antitumor efficacy and high biocompatibility via synergistic CDT, gene therapy, and cuproptosis.Conclusion This multifunctional nanosystem exhibits potent antitumor effects and low toxicity, providing a promising research direction for multimodal combinatorial cancer therapy based on CDT.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
·
基因治疗
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ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Dianbo Long,Guping Mao,Hongyi Li,Huaiwen Chen,Rui Huang,Tianyu Zhao,Zhiqi Zhang,Xiaoyi Zhao
Knee osteoarthritis (KOA) is a common joint disorder characterized by progressive cartilage degeneration. MiR-455-3p has been identified as a promising therapeutic candidate to maintain cartilage homeostasis. However, clinical application of free miR-455-3p is limited by rapid degradation, poor targeting efficiency, and off-target effects. To overcome these limitations, an injectable nanocomposite hydrogel-based miRNA delivery system consisting of a cartilage affinity nanocarrier (CANC) encapsulated within a PCL-b-PEG-b-PCL hydrogel is developed. The CANC is formulated using 50% PEGylated G5 PAMAM dendrimers to load miR-455-3p and is further modified with chondrocyte-affinity peptides (CAP) and minimal “self” peptides (MSP) to enhance cartilage targeting and evade macrophage uptake. In vitro studies demonstrated that it exhibited excellent stability, low cytotoxicity, superior cartilage penetration and chondrocyte targeting. Moreover, in vivo experiments in miR-455-3p knockout mice and a destabilization of the medial meniscus (DMM) induced KOA model confirmed that the sustained release and targeted delivery of miR-455-3p effectively rescued cartilage degeneration and prevent KOA progression. Notably, the nanocomposite hydrogel demonstrated high biocompatibility without observed cytotoxicity in major organs. This study highlights the therapeutic potential of the nanocomposite hydrogel miRNA delivery system in promoting cartilage regeneration and presents a promising approach for the development of disease-modifying osteoarthritis drugs.
研究领域:
医学
·
生物材料学
·
分子生物学
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Science Advances
·
2025
·Vol. 11
·期 47
·
IF 12.5
Wenjuan Liu,Jinlong Yang,Zibo Wei,Weiwen Kong,Zirong Dong,Yuning Wei,Jie Zhuang,Jianping Qi
Modulation of gut microbiota has emerged as a promising therapeutic strategy for inflammatory bowel disease (IBD). However, current interventions such as probiotics and fecal microbiota transplantation remain limited by insufficient safety and efficacy. To address this, we engineered commensal Lactobacillus rhamnosus (LGG) using miRNA-loaded biomimetic nanoparticles to enhance its proliferation and indole-3-carboxaldehyde production. By functionalizing bacterial extracellular vesicles (BEVs) derived from LGG with lipid nanoparticles (LNPs), we developed BEV-LNPs that exhibited enhanced targeting efficiency toward LGG compared to Escherichia coli . In vitro and in vivo studies demonstrated that BEV-LNPs showed superior stability in simulated physiological fluids and gastrointestinal environments compared to conventional LNPs. When combined with 5-aminosalicylic acid, the BEV-LNP formulation notably improved outcomes in acute and chronic colitis models, reducing inflammation, restoring epithelial barrier integrity, and promoting microbial balance. This study presents an effective strategy for colitis treatment by leveraging miRNA-loaded nanoparticles.
研究领域:
纳米医学
·
胃肠病学
·
微生物组研究
·
药物递送
·
免疫学
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Scientific Reports
·
2017
·Vol. 7
·期 1
·1-12
·
IF 4.259
Cai Chenlei,Xie Yuexia,Wu liangliang,Chen Xiaojing,Liu Hongmei,Zhou Yan,Zou Hanbing,Liu Dejun,Zhao Yanan,Kong Xianming,Liu Peifeng
Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide- co -glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo , to inhibit HCC progression. In vitro , PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent Lipofectamine TM 2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo , miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC.
研究领域:
癌症研究
·
分子生物学
·
药学
·
纳米技术
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ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Furui Jin,Danke Xu
The DNA microarray has distinctive advantages of high-throughput and less complicated operations, but tends to have a relatively low sensitivity. Catalytic hairpin assembly (CHA) is one of the most promising enzyme-free, isothermal DNA circuit for high efficient signal amplification. Here, a microarray-based catalytic hairpin assembly (mi-CHA) biosensing method has been developed to detect various miRNAs in a single test simultaneously. The target miRNA can trigger conformational transformations of hairpin-structured DNA probes on the chip surface and lead to the specific signal amplification. A significant advantage of this approach is that each duplex produced by the solid-phase CHA will be immobilized on the certain location of the chip and release fluorescent signal via the universal domain, eliminating the requirement of different fluorophores. This method has manifested a high detection sensitivity of human cancer-associated miRNAs (miR-21 and miR-155) down to 1.33 fM and promised a high specificity to distinguish single-base mismatches. Furthermore, the practicability of this method was demonstrated by analyzing target miRNAs in human serum and cancer cells. The experimental results suggest that the proposed method has high-throughput analytical potential and could be applied to many other clinical diagnosis.
研究领域:
生物技术
·
分子生物学
·
癌症研究
·
纳米技术
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BIOELECTROCHEMISTRY
·
2022
·
IF 5.76
Sasan Radfar,Reza Ghanbari,Ali Attaripour Isfahani,Halimeh Rezaei,Majid Kheirollahi
Determination of microRNAs (miRNAs) as valuable blood-borne biomarkers has attracted many scientific attentions. However, analytical methods are still restricted by miRNAs intrinsic characteristics. In this study, for the first time, novel blackberry-like magnetic DNA/FMMA nanospheres were synthesized and mounted on a gold stir-bar as signal amplification probes. To produce this strong electrochemical signal label, double strand DNAs were immobilized on gold coated magnetic nanospheres through a hybridization chain reaction followed by reversible addition-fragmentation chain-transfer polymerization, which brought a great quantity of the electroactive tags (FMMA) on the nanosphere surface. These nanospheres were then fixed on the gold stir-bar as signal probes. The magnetic DNA/FMMA nanosphere probes can be released by substituting with the newly emerging DNA fragments of catalyzed hairpin assembly products. Eventually, these signal probes were magnetically enriched on the electrode surface to produce electrochemical signal and finally, the biosensor was developed to detect miRNA-106a (model target). The suggested aptamer-based biosensor demonstrated considerable selectivity, acceptable storage stability, high specificity, and excellent performance in real sample analysis without any pretreatments. As a result, current study reveals that the developed strategy has a great potential for the early diagnosis of gastric cancer and additionally the clinical monitoring of any miRNA sequences.
研究领域:
生物化学
·
纳米技术
·
生物医学工程
·
癌症研究
·
分子生物学
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Nanoscale
·
2022
·Vol. 14
·期 12
·4538-4547
·
IF 8.307
Yanjun Yang,Chunyuan Song,Jingjing Zhang,Jie Chao,Hoang Mai Luong,Yiping Zhao,Lianhui Wang
To sensitively detect multiple and cross-species disease-related targets from a single biological sample in a quick and reliable manner is of high importance in accurately diagnosing and monitoring diseases. Herein, a surface-enhanced Raman scattering (SERS) sensor based on a functionalized multiple-armed tetrahedral DNA nanostructure (FMTDN) immobilized silver nanorod (AgNR) array substrate and Au nanoparticle (AuNP) SERS tags is constructed to achieve both multiplex detection and enhanced sensitivity using a sandwich strategy. The sensor can achieve single, dual, and triple biomarker detections of three lung cancer-related nucleic acid and protein biomarkers, i.e., miRNA-21, miRNA-486 and carcinoembryonic antigen (CEA) in human serum. The enhanced SERS signals in multiplex detections are due to the DNA self-assembled AuNP clusters on the silver nanorod array during the assay, and the experimentally obtained relative enhancement factor ratios, 150 for AuNP dimers and 840 for AuNP trimers, qualitatively agree with the numerically calculated local electric field enhancements. The proposed FMTDN-functionalized AgNR SERS sensor is capable of multiplex and cross-species detection of nucleic acid and protein biomarkers with improved sensitivity, which has great potential for the screening and clinical diagnosis of cancer in the early stage.
研究领域:
纳米技术
·
生物医学工程
·
分析化学
·
癌症诊断
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Theranostics
·
2017
·
IF 8.766
Feifei Xu,Weixian Zhou,Jianxiang Cao,Qingqing Xu,Dechen Jiang,Yun Chen
The distorted and unique expression of microRNAs (miRNAs) in cancer makes them an attractive source of biomarker. There is much evidence indicating that a panel of miRNAs, termed “miRNA fingerprints”, is more specific and informative than an individual miRNA as biomarker. Thus, multiplex assays for simultaneous quantification of multiple miRNAs could be more potent in clinical practice. However, current available assays normally require pre-enrichment, amplification and labeling steps, and most of them are semi-quantitative or lack of multiplexing capability. In this study, we developed a quasi-targeted proteomics assay for multiplexed miRNA quantification by a combination of DNA-peptide probes and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Specifically, the signal of target miRNAs (i.e., miR-21, miR-let7a, miR-200c, miR-125a and miR-15b) was converted into the mass response of reporter peptides by hybridization of miRNAs with DNA-peptide probes and subsequent tryptic digestion to release the peptides. After a careful optimization of conditions related to binding, conjugation, hybridization and multiple reaction monitoring (MRM) detection, the assay was validated for each miRNA and the limit of quantification (LOQ) for all the miRNAs can achieve 1 pM. Moreover, crosstalk between DNA-peptide probes in multiplex assay was sophisticatedly evaluated. Using this quasi-targeted proteomics assay, the level of target miRNAs was determined in 3 human breast cell lines and 36 matched pairs of breast tissue samples. Finally, simplex assay and qRT-PCR were also performed for a comparison. This approach grafts the strategy of targeted proteomics into miRNA quantification and may offer a new way for multiplexed miRNA profiling.
研究领域:
癌症生物学
·
蛋白质组学
·
分子生物学
·
生物化学
·
临床诊断
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高影响因子
危险品化学品经营许可证（带存储）