Molecular Therapy-Nucleic Acids
·
2020
·
IF 7.032
Wenjie Mao,Chong Hu,Haifeng Zheng,Jinrong Xie,Xiaorui Shi,Yarong Du,Fu Wang
MicroRNAs (miRNAs) are emerging as vital biomarkers since their abnormal expression is associated with various disease types including cancer. Therefore, it is essential to develop a sensitive and specific platform to monitor the dynamic expression of miRNAs for early clinical diagnosis and treatment. In this study, we designed a functionalized polydopamine (PDA)-based theranostic nanoprobe for efficient detection of miRNA-21 and in vivo synergistic cancer therapy. PDA was modified with polyethylene glycol (PEG) and the obtained PDA-PEG nanoparticles showed good stability in different solutions. PDA-PEG nanoparticles were loaded with fluorescein isothiocyanate (FITC)-labeled hairpin DNA (hpDNA) and an anticancer drug doxorubicin (DOX). In the absence of miRNA-21, PDA effectively quenched the fluorescence of FITC-labeled hpDNA. The presence of miRNA-21 specifically recognized hpDNA and induced the dissociation of hpDNA from PDA-PEG and subsequently recovered the fluorescence signals. Upon cellular uptake of these nanoprobes, a dose-dependent fluorescence activation and synergetic cytotoxic effect were observed due to the release of DOX and inhibition of miRNA-21 function. Furthermore, PDA-PEG-DOX-hpDNA nanoparticles can afford long-term monitoring of miRNA-21 and combined therapeutic efficacy in the nude mice bearing 4T1 tumors. Our results demonstrate the capability of PDA-PEG-DOX-hpDNA as a theranostic nanoprobe for continuously tracking of miRNAs and synergetic cancer therapy.
研究领域:
生物医学工程
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分子生物学
·
肿瘤学
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DOI
PubMed
高影响因子
Small Methods
·
2021
·Vol. 5
·期 12
·2101072
·
IF 14.188
Xiyue Xie,Zhenqiang Wang,Meizhen Zhou,Yuxin Xing,Yuhua Chen,Jixi Huang,Kaiyong Cai,Jixi Zhang
Electrochemical nanosensors by integrating functional nucleic acids and nanomaterials hold a great promise in the fast detection of biomarkers, yet the current systems possess limitations on the accessibility of target–probe and probe–electrode interactions and the repeatability of detection. Herein, a host–guest assembly strategy is developed to build redox nanosensors for an immobilization-free and ratiometric electrochemical detection system. Specifically, electroactive molecule ( E m ) guests are loaded in porous hosts of polydopamine nanoparticles (MPDA) to act as dual-signal redox reporters. Hybrid DNA probes of G-quadruplex and a single-stranded anchor DNA are installed as gatekeepers for sealing the mesopores. Thereby, miRNA triggered E m release by strand displacement reactions and the homogeneous transportation of the hosts/guests to the electrode facilitate the generation of reference signal/response signal at different potentials. Concomitantly applied NIR irradiation boosts the electron transfer from MPDA to the electrode and results in a tenfold increase in the reference signal. Finally, the sensing system through the differential pulse voltammetry method achieves a highly repeatable detection (relative standard deviation 3.8%) of miRNA with a lower detection limit (362 × 10 −15 m ). This attractive system paves the way for rational designs of advanced electrochemical biosensors and smart diagnosis.
研究领域:
生物医学工程
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分析化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2025
·
IF 10.5
Wenrui Xu,Xiaoguang Gao,Yuyan Zhai,Xiaoliang Zhang,Yingqian Wang,Rong Deng,Xiaochun Li
It remains a challenge to achieve high-sensitivity detection of tumor marker miRNA using optical refractive index (RI) sensors without nucleic acid amplification. This study proposes the photothermal effect-assisted reduced graphene oxide (rGO) biosensor that combines the photothermal effect of rGO with the rGO-based RI sensor for high-sensitivity detection of tumor marker miRNA-21. The rGO was functionalized with DNA probes capable of specifically hybridizing with the target miRNA-21. Quantitative detection of miRNA-21 was achieved by monitoring the RI change caused by the competitive hybridization of single-strand DNA (ssDNA)-functionalized AuNPs and target miRNA-21 with the DNA probes on the rGO surface. The presence of AuNPs disturbed the evanescent field on the rGO surface, thus achieving signal amplification. Furthermore, the localized photothermal effect heat induced by the interaction between rGO and pump light can effectively improve the hybridization kinetics of nucleic acid chains and achieve further signal amplification. The proposed biosensor had a high sensitivity toward the target miRNA-21, achieving a low detection limit of 4.05 fM without nucleic acid amplification. Its high specificity allowed for the recognition of single-base mismatches in miRNA-21. In addition, accurate quantification of low abundance miRNA-21 spiked into human urine samples was also successfully achieved. The photothermal effect-assisted rGO biosensor offers a promising approach for high-sensitivity detection of tumor marker miRNA without need for nucleic acid amplification.
研究领域:
生物传感器技术
·
分子诊断学
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肿瘤标志物研究
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Fangjing Mo,Jingling Wu,Min Chen,Hui Meng,Qian Han,Yingzi Fu
MicroRNAs (miRNAs) assay is of great significance for early diagnosis of diseases, so an enzyme-free “on-off-on” PEC biosensor has been developed for sensitive miRNA 141 determination. Manganese-doped cadmium sulfide coupled with zinc sulfide quantum dots (Mn: [email protected] QDs) and manganese porphyrin (MnPP) have been used as photoelectric material and photosensitizer, respectively. And a high photocurrent of approximately 70.0 μA has been obtained. Cascaded quadratic amplification strategy has been applied in the system. Mn: [email protected] QDs was characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray photoelectron spectrum (XPS) and energy dispersive X-ray spectroscopy (EDX). Photoelectrochemical and electrochemical technologies were used to monitor the fabrication process of the biosensor. The sensing platform exhibits recommendable stability and good selectivity, miRNA 141 can be accurately quantified with a linear range of 1.00 × 10 −14 to 1.00 × 10 -8 mol·L -1 and the detection limit of 3.30 fmol·L -1 . This method provides promising potential to explore sensitive detection models for various biological molecules.
研究领域:
生物技术
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医学诊断
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
TALANTA
·
2023
·
IF 6.1
Kai Zheng,Jiangfei Pan,Zipei Yu,Changqing Yi,Mei-Jin Li
We have proposed a signal dual-amplification electrochemiluminescence (ECL) strategy based on tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy) 3 2+ ) as chromophores confined with three-dimensional (3D) zinc oxalate metal−organic frameworks (Ru(bpy) 3 2+ @MOFs) for the detection of miRNA-21. The three-dimensional chromophore connectivity in zinc oxalate MOFs provided a network among Ru(bpy) 3 2+ units, shielding the chromophores from solvent molecules and resulting in high Ru(II) complex emission efficiency. Additionally, we discovered that magnetic beads (MBs) used as carrier for enriched signals contribute to enhanced ECL intensity of the chromophore. To evaluate its clinical application, we applied this method to determine the concentration of miRNA-21 solutions ranging from 1.56 to 100 nM, obtaining a calibration curve of ECL intensity versus logarithm of concentration (logC) of miRNA-21 with a high correlation coefficient. This work demonstrates the construction of a signal amplification strategy ECL biosensor for miRNA using Ru(bpy) 3 2+ @MOF systems and its application in ECL detection for analyte methodology.
研究领域:
生物化学
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分子生物学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Zengting Niu,Guotong Sun,Mingtao Tan,Shanchun Yan,Dun Jiang
Heavy metals are prevalent environmental contaminants in pest habitats. This study investigates the tolerance of Hyphantria cunea larvae to β-cypermethrin under cadmium (Cd) stress. Exposure to Cd markedly enhanced larval tolerance to β-cypermethrin. The P450 enzyme was found to be crucial in triggering this cross-tolerance. Notably, Cd exposure significantly upregulated the expression of HcCYP333A29 and HcCYP6AE184 both before and after β-cypermethrin treatment. Silencing these genes reduced the β-cypermethrin tolerance in Cd-exposed larvae. Furthermore, overexpression of HcCYP333A29 and HcCYP6AE184 significantly improved the tolerance of Sf9 cells and Drosophila to β-cypermethrin. Silencing of HcDicer-1, a key gene in the miRNA synthesis pathway, significantly diminished the β-cypermethrin tolerance in Cd-treated larvae. The miR-2739 controlled overexpression of HcCYP333A29, while miR-2854 controlled HcCYP6AE184 overexpression, both of which were essential for β-cypermethrin cross-tolerance in H. cunea larvae under Cd exposure. Collectively, Cd exposure induces cross-tolerance to β-cypermethrin in H. cunea larvae through miRNA-mediated post-transcriptional regulation.
研究领域:
环境毒理学
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分子生物学
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昆虫学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
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IF 5.6
Chenxu Peng,Mingyu Leng,Yongguang Gao,Qiumei Feng,Xiangmin Miao
In situ monitoring of intracellular microRNAs (miRNAs) often encounters the challenges of surrounding complexity, coexistence of precursor miRNAs (pre-miRNAs) and the degradation of biological enzyme in living cells. Here, we designed a novel probe encapsulated DNA tetrahedral molecular sieve (DTMS) to realize the size-selective detection of intracellular miRNA 21 that can avoid the interference of pre-miRNAs. In such strategy, quencher (BHQ-1) labeled probe DNA (S6-BHQ 1) was introduced into the inner cavity of fluorophore (FAM) labeled DNA tetrahedral scaffolds (DTS) to prepare DTMS, making the FAM and BHQ-1 closely proximate, and resulting the sensor in a "signal-off" state. In the presence of miRNA 21, strand displacement reaction happened to form more stable DNA double-stranded structure, accompanied by the release of S6-BHQ 1 from the inner cavity of DTMS, making the sensor in a "signal-on" state. The DTMS based sensing platform can then realized the size-selective detection of miRNA 21 with a detection limit of 3.6 pM. Relying on the mechanical rigidity of DTS and the encapsulation of DNA probe using DTMS, such proposed method achieved preferable reproducibility and storage stability. Moreover, this sensing system exhibited good performance for monitoring the change of intracellular miRNA 21 level during the treatment with miRNA-related drugs, demonstrating great potential for biological studies and accurate disease diagnosis.
研究领域:
分子生物学
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生物技术
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纳米技术
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细胞生物学
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分析化学
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医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT MOLECULAR MEDICINE
·
2021
·Vol. 21
·期 9
·795-805
·
IF 2.222
Yang Feng,Chun Liu-Fu,Chen Zhi-Yi
Background: Non-viral delivery systems is a promising method for gene or drug delivery. Polyethyleneimine (PEI) is a double-edged sword. It internalizes itself into the cell through endocytosis and promotes gene transfer efficiency. However, the strong positive charge also makes PEI
highly toxic to cells. Ultrasound-targeted microbubble destruction (UTMD) is a promising non-viral method for gene and drug delivery, but its efficiency still needs to be improved. Objective: The aim of this study was to explore a system that combines ultrasound with non-viral gene delivery
for the treatment of cervical cancer HeLa cells. Methods: In this study, we synthesized a kind of cationic ultrasound contrast agent(CUCA) that the physical and chemical properties, gene carrying capacity and cytotoxicity were verified. On the basis of previous studies, we further optimized
the following transfusion parameters including ultrasound parameters, microbubble concentration, plasmid concentration, cell density and other parameters. The experiment was designed to compare the following six groups: (1) Plasmid group (P group), plasmid 15 μg; (2) PEI + plasmid group
(PEI + P group),1 μl of PEI containing 10 nmol nitrogen and 1 μg of DNA containing 3 nmol phosphate for a PEI/DNA ratio equal to a nitrogen/phosphate ratio of 7 for transfection; (3) Ultrasound + plasmid group (US + P), plasmid 15 μg; (4) Ultrasound + cationic liposomal ultrasound
contrast agent + plasmid group (UTMD + P group), plasmid 15 μg and cationic liposomal ultrasound contrast agent 5%; (5) Ultrasound + cationic liposomal ultrasound contrast agent + PEI + plasmid group (UTMD + PEI + P group), PEI/DNA ratio equal to a nitrogen/phosphate ratio of 7 for transfection
and cationic liposomal ultrasound contrast agent 5%; and (6) Blank group, no treatment), The influence on Hela cells was observed under microscope, the efficiency of apoptosis was measured by flow cytometry, and cell viability was tested in CCK 8. Results: The optimized transfection parameters
can improve the transfection efficiency of ultrasound combined with C-UCA to a certain extent, but its transfection efficiency is still lower than that of branched polyethyleneimine (bPEI) 25 kDa. By investigating the effect of HeLa cells apoptosis induced by UTMD in combination with PEI mediated
survivin miRNA, we found that both PEI alone and ultrasound in combination with CUCA were able to transfect cells with survivin miRNA to effectively induce HeLa cell apoptosis. However, the synergistic effect between the two methods was not significant. Conclusion: In contrast, the combined
use of ultrasound, C-UCA and PEI may significantly reduce the transfection efficiency of UTMD and PEI, and the specific mechanism remains to be further studied.
研究领域:
肿瘤学
·
医学超声
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Xin Guo,Tian Tian,Xinchun Deng,Yang Song,Xiaoming Zhou,Erqun Song
Development of rapid and accurate detection of miRNAs in complex samples is of great significance for potential early diagnosis of disease. Herein, we report a magnetic relaxation switching (MRS)-based strategy for direct detection of miRNAs in complex samples via the assistance of signal amplification system of CRISPR/Cas13a which has the ability to specifically recognize target RNA. In the designed strategy, 30 nm-magnetic nanoparticles (MB 30 ) and 1000 nm-magnetic particles (MM 1000 ) linked by single-strand RNA 1 complexes (MB 30 -RNA 1 - MM 1000 ) were employed as signal probe. After the target miRNAs (taking miR-21 as model) recognition by CRISPR/Cas13a system, the resulted trans -cleavage degrades the MB 30 -RNA 1 -MM 1000 , releasing MB 30 which caused transverse relaxation time (T 2 ) signal change. The combination of CRISPR/Cas13a assisted signal amplification and the MRS assay achieved direct detection of miR-21 in the serum sample without extracting within 60min, with a detection limit of 0.22 pM. Moreover, the detection accuracy is confirmed by performing the detection of miR-21 using qRT-PCR. The CRISPR/Cas13a system assisted MRS assay successfully achieved accurate, simple, and rapid detection of miRNAs in complex samples, showing great potential for detection miRNAs in potential clinical applications.
研究领域:
分子生物学
·
医学诊断
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Yan Huang,Tingxiu Yan,Manyan Wu,Xiujuan Li,Xuan Gao,Yuemeng Yang,Na He,Junxian Song,Yuxia Cui,Hong Chen,Li-Ping Xu
The development of a reliable and sensitive method for the detection of myocardial infarction (MI)-specific miRNAs is of great significance in the diagnosis and management of MI. Electrochemical biosensors have emerged as a promising tool for the detection of biomolecules due to their high sensitivity, selectivity, simplicity of operation, and miniaturization. In order to further improve the sensitivity and selectivity of DNA electrochemical biosensors and meet the requirements of microRNA detection in biological samples, we fabricated a patterned superwettable gold electrode (PS-Au electrode) by mimicking the superwettable micropatterns of the desert beetle. Combining this bioinspired electrode with a DSN-assisted target recycling amplification strategy, we achieved ultrasensitive detection of myocardial infarction-specific miRNA-483 ranging from 10 aM to 100 fM with a low detection limit of 5.32 aM for miRNA-483. The electrochemical biosensor based on PS-Au electrode and DSN-assisted target recycling amplification (PSE-DTRA-EB) has good stability and specificity. Our study provides a new method for the ultrasensitive detection of MI-specific miRNAs, which may have important clinical applications in the diagnosis and prognosis of MI.
研究领域:
生物医学工程
·
分子生物学
·
电化学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Lei Liu,Mengshu Kong,Youqiang Xing,Ze Wu,Yunfei Chen
As a member of the two-dimensional transition metal dichalcogenide family, rhenium disulfide (ReS2) is a highly competitive favorite in the field of photoelectric sensors. Nevertheless, the rapid recombination of electron–hole pairs and poor electronic transmission capacity of pure ReS2 limit its wider applications. As a new attempt to optimize its inherent structure and challenge its competency boundary, in this work, a bimetallic co-chamber feeding atomic layer deposition with a precise dose regulation strategy has been used to fabricate ReS2 nanotubes (ReS2-NTs) and MoS2–ReS2 heterojunction nanotubes (MoS2–ReS2-HNTs) based on the anodic aluminum oxide template sacrifice method for the first time. These obtained NTs have at least two advantages: they have a controllable diameter (40–500 nm), definite wall thickness (1 layer to 10 layers), and desirable Mo-to-Re ratio (0 to 90%), and their electron-transfer capacity and photocurrent response can be effectively enhanced by the incorporated Mo atoms. Further experiments indicated that MoS2–ReS2-HNTs with a real Mo-to-Re ratio of 31.0% exhibits the best photocurrent response performance, by which the ultrasensitive detection of cancer-related miRNA-155 with a linear range of 10 aM to 1 nM and a detection limit of 1.8 aM is achieved.
研究领域:
材料科学
·
生物传感器
·
癌症诊断
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
·
IF 4.06
Xu Xiao,Xiaolei Hou,Wenda Shi,Chanchan Hu,Yanan Cui,Jiuli Hu,Zongfang Piao,Xiaoqin Zhu,Qingshan Li,Fan Xu
Objective: Oxymatrine has shown strong anti-cancer ability, but its mechanism is not well-studied. Methods: The inhibitory rates of oxymatrine with various concentrations (0, 1, 2, 4, 6, 8, 16, 32 mg/ml) on MCF-7 cells were detected by CCK-8. The effects of oxymatrine on the expression of miRNA-140-5P in MCF-7 cells were detected by real-time fluorescent quantitative PCR (RT-PCR). miRNA-140-5P mimics or NC mimics were transfected into cells using Lipofectamine 2000. Eventually, the cells were divided into control-group, drug-group, miRNA-140-5P mimics group, NC mimics group, and miRNA-140-5P mimics + drug group. Cell viability was detected by CCK-8 assay and apoptosis rate of each group were measured by using Flow cytometry. Western blot was carried out to detect the protein expression of TGFBR1 and FGF9. Results: Oxymatrine at various concentrations had conspicuous inhibitory effect on the proliferation of MCF-7 cells ( P<0.05 ), and the inhibitory effect of oxymatrine on MCF-7 cells showed both dose- and time-dependent manners. The relative expression of miRNA-140-5P in MCF cells was remarkably lower than that in MCF-10A. Oxymatrine could effectively promote the expression of miRNA-140-5P in MCF-7 cells, and the relative expression of miRNA-140-5P increased significantly with the increased dose of oxymatrine ( P<0.05 ). Both transfection of miRNA-140-5P mimics and oxymatrine treatment could reduce the proliferation of MCF-7 cells ( P<0.05 ), and the proliferation of cells in miRNA-140-5P mimics + drug-group was significantly lower than that of other groups ( P<0.05 ). Compared with the control-group, the protein expressions of TGFbR1 and FGF9 in low-dose, medium-dose and high-dose groups were dramatically decreased ( P<0.05 ), in a dose-dependent manner ( P<0.05 ). Conclusion: Oxymatrine inhibits proliferation and promotes cell apoptosis of breast cancer MCF-7 cells. The mechanism may contribute to the regulation of miRNA-140-5p and its target genes.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）