Small
·
2019
·Vol. 15
·期 41
·1903016
·
IF 10.856
Nan Yan,Lin Lin,Caina Xu,Huayu Tian,Xuesi Chen
Developing tumor-responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated–DNA nanodevice, based on the fluorescence nucleic acid probe and polymer-modified MnO 2 nanosheets, for glutathione (GSH)-gated miRNA-21 signal amplification and GSH-activated magnetic resonance (MR) imaging–guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false-positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor-responsive hydroxyl radical ( · OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase-like activity and glucose oxidase–like activity with the performance of O 2 production and glucose consumption. This is the first time to fabricate a tumor-responsive theranostic DNA nanodevice with tumor-specific signal amplification of microRNA and GSH-activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.
研究领域:
生物医学工程
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纳米技术
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诊疗学
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分子生物学
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Duo Chen,Na Chen,Fangning Liu,Yiming Wang,Huageng Liang,Yanbing Yang,Quan Yuan
Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I–III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.
研究领域:
生物医学工程
·
纳米技术
·
癌症诊断
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电化学
·
即时检测设备
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2017
·Vol. 142
·期 15
·2796-2804
·
IF 3.885
Zhenqiang Wang,Jixi Zhang,Feng Chen,Kaiyong Cai
The combination of fluorophore-labelled single-strand DNA probes and nanomaterial quenchers has shown great potential in miRNA detection. The development of advanced detection systems by understanding and controlling the fluorescence quenching/recovery via nanoquenchers’ microstructures and local morphologies is an attractive area warranting further investigations. Inspired by nanopore sequencing, we present a novel miRNA sensing strategy using fluorophore-labeled DNA as probes and a type of large-pore-sized mesoporous polydopamine nanoparticles (MPDA-L, 70 nm in diameter) as fluorescence quenchers. It is revealed that the quenching efficiency of MPDA-L towards the fluorophore labelled on the probe, reached more than 99% at a relatively low particle concentration. Moreover, the mesopores effectively protected the probe DNA from cleavage by DNase I which was used for signal amplification. Sensitive detection of miRNA with a low detection limit of 32–40 pM, as well as a linear detection range of up to 5 nM, was realized by the mesopore effects via a greatly improved differential affinity of ssDNA and the probe–miRNA heteroduplex toward the surface of nanoquenchers. Interestingly, enhanced DLVO (Derjaguin–Landau–Verwey–Overbeek) repulsion generated inside the pore surface by the negative surface–curvature effect correlates with the improved duplex detachment and fluorescence recovery. The developed strategy can be successfully applied to quantify down-regulated let-7a and up-regulated miRNA-21 in different types of cancer cells by using total RNA samples from cell lysate. These findings are expected to inspire strategies and pave a way for utilizing porous nanomaterials for constructing miRNA detection systems.
研究领域:
纳米技术
·
生物医学工程
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2019
·
IF 5.256
Lina Wu,Yingfei Wang,Rong He,Yue Zhang,Yuling He,Chao Wang,Zhenda Lu,Ying Liu,Huangxian Ju
Despite the great success of fluorescence sensing array application in bioanalysis , the photo-quenching problem accompanied with high surface fluorophore density has become the bottleneck for its further sensitivity improvement. Herein, a fluorescence polyethylene glycol (PEG) hydrogel array was developed for highly sensitive microRNA detection based on interfacial cation exchange amplification coupled with DNA hybridization chain reaction (HCR). The carboxylate PEG hydrogel array was fabricated on glass slide via photo polymerization and modified with miRNA capture probe, target miRNA binding triggered HCR in hydrogel with biotin labelled DNA probes to generate numerous DNA polymer chains where biotinylated CdS QDs were subsequently conjugated with a streptavidin bridge. Interfacial cation exchange amplification was triggered in hydrogel upon the introduction of Ag + and Rhod-5N, and abundant Cd 2+ was released from CdS to bind with Rhod-5N for substantial fluorescence enhancement. The aqueous-like environment of hydrogel eliminated the fluorescence quenching and simplified experiment process by performing cation exchange reaction at interface with direct result. The linear range for model target miRNA-21 was 1 fM to 500 pM with a detection limit of 0.835 fM. Taking advantage of the nonfouling property of PEG hydrogel, direct quantification of miRNA-21 was achieved from crude cancer cell lysates with a detection limit down to 10 equivalent cells. The expressions of circulating miRNA-21 in clinical serum samples were also assessed with comparable results from RT-PCR. The developed hydrogel array provides a universal platform for highly sensitive fluorescence sensing, and would benefit clinical non-invasive disease diagnosis.
研究领域:
生物化学
·
生物技术
·
分析化学
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分子生物学
·
临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Wenrui Ma,Lulu Liu,Xu Zhang,Xingfei Liu,Yi Xu,Shunbo Li,Muling Zeng
Developing sensitive and miniaturized biosensors for the detection of microRNAs (miRNAs) is highly desirable due to their association with early cancer diagnosis and prognosis. Here, a new microfluidic-based biosensor, combined with multifunctional nanosurface and DSN-assisted target recycle amplification strategy, is designed for the detection of miRNA-21. The design of nanosurface includes gold nanoparticles on porous anodic aluminum oxide (AAO) for surface enhanced Raman scattering (SERS) substrate, Au MBA @Ag core-shell nanoparticles for SERS nanotags and single-stranded DNA (ssDNA) in between for miRNA capture and nanotags immobilization. When the target miRNA is present near the nanosurface, it will be captured by ssDNA via hybridization reaction. Then, triggered by the DSN-assisted target recycle process, the freshly formed DNA/miRNA heteroduplexes are cleaved by DSN enzyme into DNA fragments and single-strand miRNA. The SERS nanotags are also dissociated from the nanosurface, leading to decrease of SERS signal. The cleaved target miRNA can be captured and SERS nanotags are released again in the next cycle, resulting in amplification of detection signal. To improve the accuracy of this biosensor, the functionalized AAO membrane is subdivided into two groups - AAO/Au array linked with encoded core-shell SERS nanotags acting as a reactor and primary detector and AAO/ [email protected] array serving as a collector and secondary detector for the dissociative SERS nanotags from the reactor. The decrease of SERS signal in primary detector and increase of signal in secondary detector ensures the accuracy and it is called dual-SERS detection strategy. The detection of miRNA-21 can be achieved with only 30 μL sample and 10 μL enzyme and a wide linear range of 10 fM∼10 nM is obtained. In addition, the microfluidic dual-SERS detection strategy can greatly reduce the possibility of false positive or false negative in single detection mode and it can be applied to the simultaneous detection of multiple miRNAs via integrating different probes.
研究领域:
生物传感器
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微流控技术
·
表面增强拉曼散射（SERS）
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纳米技术
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癌症诊断
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）