MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 7
·1-9
·
IF 6.232
Qian Wenhui,Miao Zhaoyi,Zhang Xiao-Jing,Yang Xiao-Tong,Tang Ying-Ying,Tang Yu Ying,Hu Lin Yu,Li Su,Zhu Dong,Cheng Haibo
An integrated aptamer macroarray functionalized with reduced graphene oxide (rGO) to specifically capture and sensitively detect cancer cells is reported. The capture for cancer cells is based on effective recognition of the modified rGO surface through the aptamer against epithelial cell adhesion molecule (EpCAM). The rough structure of rGO enhances morphologic interactions between rGO film interface and the cancer cells, while super-hydrophilicity of modified rGO hinders nonspecific cell capture. The synergistic interactions offer the aptamer macroarray high efficiency of cancer cell capture. By means of a turn-on fluorescence strategy based on the conformation change of the aptamer induced by the target recognition, the enriched cancer cells can be directly read out at excitation/emission wavelengths of 550/680 nm without washing, separation, and dying steps. The working range is 1 × 10 2 to 2 × 10 4 cells per mL with a detection limit of 22 cells per mL. The results indicate that the aptamer macroarray has a considerable foreground for early diagnosis, therapy, and monitoring of cancer.
Graphical abstract
研究领域:
生物医学工程
·
分子诊断
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Materials
·
2023
·Vol. 16
·期 8
·3065
·
IF 3.4
Mengting Qi,Meilin Ruan,Jinjin Liang,Zhengtao Zhang,Chaohui Chen,Yiping Cao,Rongxiang He
A 3D network capture substrate based on poly(lactic-co-glycolic acid) (PLGA) nanofibers was studied and successfully used for high-efficiency cancer cell capture. The arc-shaped glass micropillars were prepared by chemical wet etching and soft lithography. PLGA nanofibers were coupled with micropillars by electrospinning. Given the size effect of the microcolumn and PLGA nanofibers, a three-dimensional of micro-nanometer spatial network was prepared to form a network cell trapping substrate. After the modification of a specific anti-EpCAM antibody, MCF-7 cancer cells were captured successfully with a capture efficiency of 91%. Compared with the substrate composed of 2D nanofibers or nanoparticles, the developed 3D structure based on microcolumns and nanofibers had a greater contact probability between cells and the capture substrate, leading to a high capture efficiency. Cell capture based on this method can provide technical support for rare cells in peripheral blood detection, such as circulating tumor cells and circulating fetal nucleated red cells.Keywords:cancer cells;nanofibers;micropillar;mesoscopic interface;microchip
研究领域:
生物医学工程
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癌症研究
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纳米技术
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微流控
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Yang Xiao,Zhiyi Zhou,Yifan Zuo,Xueyuan Wu,Yuping Liu,Yichen Li,Yuetong Gao,Xiashu Zhang,Yu Wang,Lili Hu,Chenglin Li
Background The technology of capturing circulating tumor cells (CTCs) plays a crucial role in the diagnosis, evaluation of therapeutic efficacy, and prediction of prognosis in lung cancer. However, the presence of complex blood environment often results in severe nonspecific protein adsorption and interferences from blood cells, which negatively impacts the specificity of CTCs capture. There is a great need for development of novel nanomaterials for CTCs capture with prominent anti-nonspecific adsorptions from proteins or blood cells. Results We present a novel immune magnetic probe Fe 3 O 4 @(PEI/AA) 4 @Apt. The surface of Fe 3 O 4 particles was modified with four layers of PEI/AA composite by layer-by-layer assembly. Furthermore, aptamers targeting epithelial marker EpCAM (SYL3C) and mesenchymal marker CSV (ZY5C) were simultaneously connected on Fe 3 O 4 @(PEI/AA) 4 to improve the detection of different phenotypic CTCs and reduce false negatives. The results demonstrated that the (PEI/AA) 4 coatings not only minimized non-specific protein adsorptions, but also significantly reduced the adsorption rate of red blood cells to a mere 1 %, as a result of which, the Fe 3 O 4 @(PEI/AA) 4 @Apt probe achieved a remarkably high capture efficiency toward CTCs (95.9 %). In the subsequent validation of clinical samples, the probe was also effective in capturing rare CTCs from lung cancer patients. Significance and novelty A (PEI/AA) polymerized composite with controllable layers was fabricated by layer-by-layer self-assembly technique, which displayed remarkable anti-nonspecific adsorption capabilities toward proteins and cells. Importantly, Fe 3 O 4 @(PEI/AA) 4 @Apt probe significantly improved CTCs capture purity in lung cancer patients to 89.36 %. For the first time, this study combined controllable (PEI/AA) layers with magnetic separation to innovatively build a resistant interface that significantly improves the specific capture performances of CTCs, broadening the application of this polymerized composite.
研究领域:
生物医学工程
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纳米技术
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癌症诊断
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2023
·Vol. 12
·期 9
·12364
·
IF 16
Jie He,Hengyu Li,John Mai,Yuqing Ke,Chunhui Zhai,Jiao Jiao Li,Lai Jiang,Guangxia Shen,Xianting Ding
Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non-EV components in clinical samples. Herein, we present a MEmbrane-Specific Separation and two-step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin-coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2-positive breast cancer, triple-negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.
研究领域:
生物技术
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医学诊断
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癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2021
·
IF 10.618
Yuan Zhao,Jie Yao,Zhenglong Wu,Han Liu,Wangwang Zheng
Strong and stable electrochemical beacons are critical for the achievement of sensitive and reliable electroanalysis applications. In this work, the electrochemical oxidation performance of AuPt NPs was studied and firstly found to be largely enhanced under light illumination. Plasmonic AuPt NPs collected light energy after local surface plasmon resonance (LSPR) excitation and generated much more holes to participate in the electrochemical oxidation process of Pt 0 in AuPt NPs. AuPt NPs with the electrochemical oxidation peak at around −0.7 V were utilized as detection probes for the fabrication of ratiometric electrochemical aptasensor , by introducing Co-MOF/Fe 3 O 4 /Ag nanosheets (NSs) with the electrochemical oxidation peak at 0.1 V as reference beacons. The aptamers of epithelial cell adhesion molecule (EpCAM) modified AuPt NPs were assembled with Co-MOF/Fe 3 O 4 /Ag NSs, which generated strong detection and reference signals at −0.7 V and 0.1 V, respectively. The high affinity between EpCAM and aptamers induced the separation of AuPt NPs from Co-MOF/Fe 3 O 4 /Ag NSs, resulting in the decrease of detection signal at −0.7 V and unchanged reference signal at 0.1 V. A ratiometric electrochemical aptasensor was achieved for the sensitive and reliable quantification of EpCAM in the range from 100 pg/mL to 100 ng/mL. The limit of detection (LOD) was calculated to be 13.8 pg/mL for EpCAM. Plasmon-driven electrochemical oxidation enhancement principle provides the possibility for the design and fabrication of more strong and anti-interference electroactive plasmonic metal-Pt composite nanostructures for the electroanalysis applications.
研究领域:
生物医学工程
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分析化学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Xiaoshuo Zhang,Rui Dai,Faqiong Zhao,Baizhao Zeng
Background Epithelial cell adhesion molecules (EpCAM) protein is one of the most frequently and intensely studied tumor-associated antigens because of its overexpression in most cancer cells. Thus, it is regarded as a tumor biomarker associated with a wide variety of carcinomas and reflects the existence and growth of tumors in the human body. It is highly required to detect low concentrations of EpCAM in early stage for ensuring human health. Results In this study, a novel sandwich electrochemiluminescence (ECL) aptasensor was developed for EpCAM detection. Wherein oxalate-based Zn-MOF supported tris(2,2′-bipyridyl)ruthenium (II) (Ru(bpy) 3 2+ @Zn-MOF) was used as luminophore and gold nanoparticle modified o-phenylenediamine (PoPD@Au NPs) as quencher. The 3D Ru(bpy) 3 2+ @Zn-MOF generated self-enhanced ECL without additional co-reactants. Furthermore, it remained stable and had short electron transfer distance, ensuring high and stable ECL signal. The ECL signal could be effectively quenched by PoPD@Au NPs through resonance energy transfer (RET) and electron transfer (ET), due to its absorption spectrum overlapping with the ECL emission spectrum of Ru(bpy) 3 2+ @Zn-MOF. In the presence of EpCAM, the aptamer acted as a linker between the luminophore and quencher, forming a sandwich structure that had reduced ECL intensity. Under optimal conditions, EpCAM could be sensitively detected over the range of 1 pg mL -1 -100 ng mL -1 , with a detection limit of 0.34 pg mL -1 . Significance This work developed a ECL aptasensor with self-enhanced Ru(bpy) 3 2+ @Zn-MOF luminophore for EpCAM detection. The ECL system was simple, but ultrasensitive for EpCAM monitoring, thanks to the ECL-RET and ET between Ru(bpy) 3 2+ @Zn-MOF and PoPD@Au NPs. It also could be applied to detect other biomolecules by replacing the aptamer, offering significant potential in disease diagnosis.
研究领域:
生物传感器
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癌症诊断
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分析化学
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纳米材料
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生物分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2015
·
IF 12.881
Jingxin Meng,Pengchao Zhang,Feilong Zhang,Hongliang Liu,Junbing Fan,Xueli Liu,Gao Yang,Lei Jiang,Shutao Wang
The advanced nanobiochips have been widely employed in diagnosing some high incidence of diseases because of their portable, low-cost, and highly sensitive features. However, the subsequent disposal of these wastes remains unexposed, probably giving rise to serious environmental pollution and health risks similar to traditional biomedical waste. Here, we have presented a TiO2 nanosisal-like coating for disposing nanobiochip waste via the photoresponsive self-cleaning features of the nanobiochip, demonstrated by the nanochips of cancer detection. Moreover, the high specificity and sensitivity of nanochips can be maintained by integrating unique nanostructured coatings (i.e., nanosisal-like coating) with specific recognition molecules (i.e., anti-EpCAM). Therefore, this study will provide a promising strategy for the design and management of practical nanobiodevices, thereby eliminating the old path “pollute first, clean up later”.
研究领域:
纳米技术
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生物医学工程
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环境科学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 28
·6951-6962
·
IF 4.157
Wang Huai-Song,Xia Xingya,Wang Yingming,Lyu Weiping,Sang Mangmang,Gu Congcong,Liu Wenyuan,Zheng Feng
Epithelial-mesenchymal transition (EMT) is implicated in the pathological processes of cancer metastasis and drug resistance. Anti-cancer drugs may also potentially lead to EMT, resulting in their reduced therapeutic effect. Therefore, the combination of these anti-cancer drugs with anti-EMT agents has been promoted in clinic. Screening anti-EMT drugs and evaluation of EMT process are highly dependent on EMT biomarkers on cell membrane. At present, the detection of EMT biomarker is mainly by Western blot method, which is time-consuming and complicated. In this work, for effectively screening anti-EMT drugs by evaluation of the EMT process, a type of aptamer probe based on aggregation-induced emission (AIE) was designed. The aptamer SYL3C was employed to target the EMT biomarker EpCAM on cell membrane. Two fluorophores, FAM and tetraphenylethene (TPE, an AIE dye), were modified at the two ends of SYL3C, respectively. This aptamer probe (TPE-SYL3C-FAM) can monitor the EpCAM expression, which can be recovered by anti-EMT drugs. By observation of the change in TPE emission intensity, the anti-EMT effect of drugs can be evaluated. The FAM emission was used as internal reference to reduce environmental interferences. This probe can be potentially used to screen anti-EMT agents as anti-cancer adjuvant drugs with high throughput. Graphical abstract
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 6
·2383-2393
·
IF 5.251
Wanyun Song,Xinyi Li,Yuquan Zhao,Chaoying Liu,Junying Xu,Huiyu Wang,Tao Zhang
The capture of circulating tumor cells (CTCs) plays a crucial role in the early diagnosis, personalized treatment and postoperative evaluation of malignant tumors. In this study, UV-curable coating technology was combined with antibody immobilization to enable CTC captures on poly(methyl methacrylate) (PMMA) substrates. Controlled amounts of carboxyl groups and polyethylene glycol (PEG) segments were introduced into the coating formulation to facilitate immobilization of antibodies and block non-specific protein adsorption, respectively. Then, anti-EpCAM antibodies were immobilized on functionalized, coated PMMA substrates by EDC/NHS chemistry. Multiple physical, chemical and biological properties were investigated, including hydrophilicity, protein adsorption, platelet adhesion and anticoagulant properties. Thereafter, optimized coatings were applied on the inner wall of PMMA tubes, followed by immobilization of anti-EpCAM antibodies. After perfusion of the tubes with whole blood, enriched with SGC7901 gastric cancer cells that overexpress EpCAM antigens, rapid and efficient capture of the tumor cells was observed. These results provide a basis for further development of devices for the selective capture and enrichment of CTCs, using small blood volumes.
研究领域:
生物医学工程
·
癌症研究
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材料科学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Dou Wang,Ruihua Dong,Xuedong Wang,Xingyu Jiang
Clearing circulating tumor cells (CTCs) that are closely related to cancer metastasis and recurrence in peripheral blood helps to reduce the probability of cancer recurrence and metastasis. However, conventional therapies aiming at killing CTCs always cause damage to normal blood cells, tissues, and organs. Here, we report a flexible electronic catheter that can capture and kill CTCs via irreversible electroporation (IRE) with high efficiency. The flexible electronic catheter is assembled from nanofibers (NFs) with liquid metal–polymer conductor (MPC) electrodes. The NFs were modified with an epithelial cellular adhesion molecule (EpCAM) antibody on the surface to improve specific biorecognition and cell adhesion. Whole-body blood can be screened by the catheter repeatedly, during which the EpCAM antibody on a nanofiber can enrich CTCs to the surface of the catheter. Taking advantage of the high specific surface area, the capture efficiency of NF-based catheters for CTCs is 25 times higher than previously reported cases. Furthermore, the number of nonspecifically captured WBCs is less than 10 per mm2 areas of the catheter, compared to their original large number of 4–11 × 106 mL–1 of whole blood, showing good specificity of the flexible electronic catheter. The flexible and biocompatible MPC electrodes have a high killing efficiency of 100% for the captured CTCs in a rabbit model. No noticeable hematologic index and morphological changes of the vessels and major organs were observed, indicating that this electronic catheter had good biocompatibility. The present functional electronic catheter offers an alternative strategy for improving the efficiency of clinical cancer therapy
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS
·
2019
·Vol. 19
·期 8
·1879
·
IF 3.031
Jianguo Xu,Xinxin Wang,Chao Yan,Wei Chen
A new electrochemical immunosensor for cancer cell detection based on a specific interaction between the metastasis-related antigen of epithelial cell adhesion molecule (EpCAM) on the cell membrane and its monoclonal antibody (Anti-EpCAM) immobilized on a gold electrode has been developed. The amino-terminated polyamidoamine dendrimer (G6 PAMAM) was first covalently attached to the 3-mercaptopropionic acid (MPA)-functionalized gold electrode to obtain a thin film, and then completely carboxylated by succinic anhydride (SA). Next, the Anti-EpCAM was covalently bound with the G6 PAMAM to obtain a stable recognition layer. In the presence of the EpCAM expressing hepatocellular carcinomas cell line of HepG2, the specific immune recognition (Anti-EpCAM/EpCAM) led to an obvious change of the electron transfer ability. The properties of the layer-by-layer assembly process was examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The final determination of HepG2 cells was performed in the presence of the reversible [Fe(CN)6]3−/4−redox couple using impedance technique. Based on the advantages of PAMAM nanomaterial and immune reaction, a linear response to HepG2 cells ranging from 1 × 104to 1 × 106cells mL−1with a calculated detection limit of 2.1 × 103cells mL−1was obtained. We expect this method can provide a potential tool for cancer cell monitoring and protein expression analysis.Keywords:label-free;immunosensor;polyamidoamine dendrimer;epithelial cell adhesion molecule (EpCAM), electrochemical impedance spectroscopy (EIS)
研究领域:
生物传感器
·
电化学
·
癌症研究
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Nayun Kim,Junhye Kwon,Ui Sup Shin,Joohee Jung
Colorectal cancer (CRC) is associated with high incidence and mortality rates. Targeted therapies for CRC cause various adverse effects, necessitating the development of novel approaches to control CRC progression. In this milieu, we investigated the anti-CRC effects of fisetin, a natural plant flavonoid. Cytotoxicity was performed in CRC patient-derived organoids (30 T and 33 T). Fisetin-induced tumor growth was evaluated in a CRC patient-derived organoid xenograft (PDOX) model. RNA sequencing, immunohistochemistry, and western blotting were performed subsequently. Fisetin significantly decreased organoid viability in a dose-dependent manner. In the PDOX model, fisetin significantly delayed tumor growth, showing a decrease in Ki-67 expression and the induction of apoptosis. In tumor tissues, four genes were identified as differentially expressed between the control and fisetin-treated groups. Among these, A-kinase anchoring protein 12 ( AKAP12 ) level was significantly increased by fisetin treatment (fold change > 2, p < 0.05). Notably, fisetin significantly inhibited vascular endothelial growth factor (VEGF) and epithelial cell adhesion molecule (EpCAM) via upregulation of AKAP12. Our results demonstrate the upregulation of AKAP12 mRNA and inhibition of angiogenesis by fisetin as a therapeutic strategy against CRC.
研究领域:
肿瘤学
·
药理学
·
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）