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NEW JOURNAL OF CHEMISTRY · 2021 ·Vol. 45 ·期 12 ·5551-5560 · IF 3.591

Cellulose nanocrystalline and sodium benzenesulfonate-doped polypyrrole nano-hydrogel/Au composites for ultrasensitive detection of carcinoembryonic antigen

Xiangrong Huang,Zhuoyao Ni,Haiping Su,Yazhuo Shang,Honglai Liu,Yifan He,Hong Meng,Yinmao Dong

Precise and early detection of carcinoembryonic antigen (CEA) as a tumor marker of various cancers provides the best hope for the treatment of the deadly malignancy. Thus, the design of an immunosensor with high sensitivity is significant for early and accurate detection of CEA. In this work, a novel label-free electrochemical immunosensor was designed for the detection of CEA based on a nanostructured conductive polymer hydrogel loaded with gold nanoparticles (AuNPs). The hydrogel (BSNa-CNC-PPy) was simply prepared via in situ synthesis of polypyrrole (PPy) using cellulose nanocrystalline (CNC) and sodium benzenesulfonate (BSNa) as dopants to participate in the formation of the three-dimensional nano-hydrogel. AuNPs were further electrodeposited on the surface of BSNa-CNC-PPy gel-modified glassy carbon electrode (GCE). The immunoassay platform was obtained when the AuNPs/BSNa-CNC-PPy gel/GCE was incubated with anti-CEA and blocked by bovine serum albumin in succession. By combining the advantages of biocompatibility, nanostructure, outstanding hydrophilicity, excellent film-forming ability as well as the gelatinization of CNC, the CNC-PPy gel/GCE showed high conductivity (electroactive surface area), strong hydrophilicity, and film-forming property. The introduction of BSNa improved the conductivity of BSNa-CNC-PPy gel/GCE further due to enhanced interchain charge transport of PPy chains. The BSNa-CNC-PPy gel/GCE showed a 214% increase in electroactive surface area and the dried BSNa-CNC-PPy gel demonstrated a large specific surface area (76.59 m2 g−1), which were superior to those of existing conducting polymer hydrogels. AuNPs were apt to immobilize a mass of antibodies and accelerate electron transfer. The fabricated CEA-detecting immunosensor displayed a wide linear detection range of 1 fg mL−1 to 200 ng mL−1 and an ultralow limit of detection of 0.06 fg mL−1 (at a signal to noise ratio of 3). In addition to high sensitivity, the immunosensor exhibited excellent stability, high selectivity, good reproducibility, and strong reliability for real sample analysis. The proposed label-free electrochemical immunosensor has potential to be a diagnostic tool in clinical analysis of CEA.

CAS / MDL: 98-10-2
研究领域: 材料科学 · 纳米技术 · 分析化学 · 生物传感器 · 癌症诊断
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BIOELECTROCHEMISTRY · 2021 · IF 5.373

Sandwich electrochemical carcinoembryonic antigen aptasensor based on signal amplification of polydopamine functionalized graphene conjugate Pd-Pt nanodendrites

Fenglin Zhang,Zhiguang Liu,Yujie Han,Lifang Fan,Yujing Guo

Carcinoembryonic antigen (CEA) is considered as a disease biomarker, which is related to various cancers and tumors in the human bodies. Sensitive detection of CEA is significant for clinical diagnosis and treatment. Herein, we proposed an electrochemical aptasensor for CEA detection based on the amplification driven by polydopamine functional graphene and Pd-Pt nanodendrites ( [email protected] /Pd-PtNDs), conjugated hemin/G-quadruplex (hemin/G4), which possess mimicking peroxidases activity. Firstly, [email protected] was modified on the electrode surface for fixing CEA aptamer 1 (Apt1). Then, [email protected] /Pd-PtNDs with large surface area served as matrix for immobilization of hemin/G4 to obtain the secondary aptamer. In virtue of the sandwich-type specific reaction between CEA and the corresponding aptamers, the second aptamer was captured on the sensing interface, which can catalyze the oxidation of signal probe hydroquinone (HQ) with H 2 O 2 and amplify current signal. Furthermore, the electrochemical signals of HQ were proportional with CEA concentrations. Under the optimal conditions, a dynamic response range from 50 pg/mL to 1.0 μg/mL and a detection limit of 6.3 pg/mL for CEA were obtained. Moreover, the proposed strategy represented satisfactory sensitivity and stability, and showed a good precision in real samples application.

CAS / MDL: 16941-12-1 10025-99-7
研究领域: 生物传感器 · 分析化学 · 纳米技术 · 癌症诊断
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

Enhanced catalytic amplification of mesoporous bismuth-gold nano-electrocatalyst triggering efficient capture of tumor marker

Lan Jiang,Peiwu Chen,Ling Zha,Jinyao Liu,Dong Sun,Chenyu Dai,Yuhao Li,Yuqing Miao,Ruizhuo Ouyang

A new sandwich-type electrochemical immunosensor for the sensitive detection of carcinoembryonic antigen (CEA) was originally developed using a unique bismuth (Bi)-gold (Au) nano-electrocatalyst triggering efficient capture of tumor marker, where the nano-electrocatalyst was obtained by implanting Au nanoparticles (Au NPs) inside the mesoporous NBiOF nanospheres ( [email protected] NSs) for the purpose to marker secondary antibody (Ab 2 ) and amplify the response signal through electrochemically catalyzing the reduction of hydrogen peroxide. The synergistic interaction between NBOF NSs and Au NPs endowed the as-received [email protected] nano-electrocatalyst with large electrocatalytic active surface area and powerful signal amplification function as upper sandwich layer to conjugate Ab 2 . The multi-walled carbon nanotubes sparkled with Au nanostars served as the lower sandwich layer to capture the primary antibody (Ab 1 ), which enhanced the interfacial electron transport and the load capacity of Ab 1 as a result of increasing the sensing response of the designed immunosensor based on the sandwich-type Ab 1 -CEA-Ab 2 interaction. Such immunosensor proposed on the above double signal amplification strategy efficiently detected the target CEA in a wide concentration range from 100 fg mL −1 to 200 ng mL −1 . The detection limit was as low as 9.57 fg mL −1 with excellent specificity and reproducibility. The satisfactory results in analyzing human serum samples indicate the potential application of this new immunosensor in early clinical diagnosis of cancer and the evaluation of treatment efficiency.

研究领域: 电化学 · 纳米技术 · 生物传感器 · 癌症诊断
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Frontiers in Chemistry · 2023 · IF 5.5

Probe-integrated electrochemical immunosensor based on electrostatic nanocage array for reagentless and sensitive detection of tumor biomarker

Chen Dong,Luo Xuan,Xi Fengna

Sensitive detection of tumor biomarkers is crucial for early diagnosis and prognosis evaluation of cancer. Owing to no need of labelled antibody, formation of sandwich immunocomplexes and additional solution-based probe, probe-integrated electrochemical immunosensor for reagentless detection of tumor biomarkers is highly desirable. In this work, sensitive and reagentless detection of a tumor biomarker is realized based on fabrication of a probe-integrated immunosensor by confining redox probe in electrostatic nanocage array modified electrode. Indium tin oxide (ITO) electrode is employed as the supporting electrode because it is cheap and easily available. The silica nanochannel array consisted of two layers with opposite charges or different pore diameters was designated as bipolar films (bp-SNA). In this work, Electrostatic nanocage array is equipped on ITO electrode by growth of bp-SNA with two layered nanochannel array having different charge properties including a negatively charged silica nanochannel array (n-SNA) and a positively charged amino-modified SNA (p-SNA). Each SNA can be easily grown with 15 s using electrochemical assisted self-assembly method (EASA). Methylene blue (MB) is applied as the model electrochemical probe with positive charge to be confined in electrostatic nanocage array with stirring. The combination of the electrostatic attraction from n-SNA and the electrostatic repulsion from p-SNA endows MB with highly stable electrochemical signal during continuous scanning. When the amino groups of p-SNA are modified using the bifunctional glutaraldehyde (GA) to introduce aldehydes, the recognitive antibody (Ab) of the most commonly used tumor biomarker, carcinoembryonic antigen (CEA), can be covalently immobilized. After the non-specific sites are blocked, the immunosensor is successfully fabricated. As the formation of antigen-antibody complex decreases electrochemical signal, the immunosensor can achieve reagentless detection of CEA ranged from 10 pg/mL to 100 ng/mL with a low limit of detection (LOD, 4 pg/mL). Determination of CEA in human serum samples is realized with high accuracy.

研究领域: 生物医学工程 · 分析化学 · 癌症诊断
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ANALYTICAL BIOCHEMISTRY · 2022 · IF 3.191

Ratiometric electrochemical aptasensor for the sensitive detection of carcinoembryonic antigen based on a hairpin DNA probe and exonuclease I-assisted target recycling

Huikai Ma,Ping Wang,Yaoyao Xie,Jinghan Liu,Wei Feng,Sanqiang Li

A novel ratiometric electrochemical aptasensor was constructed for the detection of carcinoembryonic antigen (CEA) based on a hairpin DNA (hpDNA) probe and exonuclease Ⅰ (Exo Ⅰ)-assisted target recycling amplification strategy. A thiolated methylene blue (MB)-labeled hpDNA as the internal control element was fixed on the surface of the gold nanoparticles (AuNPs)-modified gold electrode (AuE) through Au–S bonds. A ferrocene (Fc)-modified aptamer DNA (Fc-Apt) was partially hybridized with hpDNA to form a Fc-Apt/hpDNA duplex. Due to the specific recognition of Fc-Apt to CEA, the presence of CEA caused dissociation of Fc-Apt from the duplex, and further triggered the degradation process of Exo Ⅰ and recycling of CEA. Hence, the Fc tags were released from the electrode surface and the oxidation peak current of Fc (I Fc ) decreased while that of MB (I MB ) remained stable owing to the distance between MB tags and the electrode unchanged. A linear relationship was observed between I Fc /I MB and the logarithm of CEA concentration from 10 pg mL −1 to 100 ng mL −1 with a detection limit of 1.9 pg mL −1 . Moreover, the developed aptasensor had been applied to detect CEA in diluted human serum with satisfactory results, indicating its great potential in practical applications.

研究领域: 分析化学 · 生物传感器 · 电化学 · 癌症诊断
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MICROCHIMICA ACTA · 2024 ·Vol. 191 ·期 9 ·1-9 · IF 5.3

Rapid photothermal assay for ultrasensitive point-of-care detection of tumor markers based on a filter membrane

Liu Shendong,Chen Xinlian,Zhao Hong,Lin Tianran,Hou Li,Zhao Shulin

An ultrasensitive photothermal assay was designed for point-of-care testing (POCT) of tumor markers based on a filter membrane. Firstly, Cu 2-x Se was successfully encapsulated in liposome spheres with biotin on the surface and connected to carcinoembryonic antigen (CEA) aptamer with 3'end modified biotin by streptavidin. Secondly, the CEA antibody was successfully modified on the surface of the nitrocellulose membrane through simple incubation. Finally, the assay process was completed using a disposable syringe, and the temperature was recorded using a handheld infrared temperature detector. In the range 0–50 ng mL −1 , the temperature change of the nitrocellulose membrane has a strong linear relationship with CEA concentration, and the detection limit is 0.097 ng mL −1 . It is worth noting that the entire testing process can be easily performed in 10 min, much shorter than traditional clinical methods. In addition, this method was successfully applied to the quantitative determination of CEA levels in human serum samples with a recovery of 96.2–103.3%. This rapid assay can be performed by “one suction and one push” through a disposable syringe, which is simple to operate, and the excellent sensitivity reveals the great potential of the proposed strategy in the POCT of tumor biomarkers. Graphical Abstract

研究领域: 生物医学工程 · 分析化学 · 即时诊断 · 癌症生物标志物
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 8 ·1-8 · IF 5.479

A voltammetric immunoassay for the carcinoembryonic antigen using silver(I)-terephthalate metal-organic frameworks containing gold nanoparticles as a signal probe

Liu Jianbo,Shang Yonghui,Zhu Qiuyan,Zhang Xinxue,Zheng Jianbin

A voltammetric immunoassay for the carcinoembryonic antigen (CEA) was developed using silver metal-organic frameworks (Ag-MOFs) as a signal probe. The Ag-MOFs contained a substantial amount of Ag(I) whose electrochemical signal was relatively stable. Therefore, the Ag-MOFs were viable signal probes. The signal can be detected without previous acid dissolution and preconcentration steps. This simplifies the detection steps and reduces the detection time. If CEA binds to its antibody on the modified electrode, the signal for Ag(I) becomes reduced. Measurements were best performed at a potential as low as 0.07 V (vs. SCE) which made the electrode hardly sensitive to potential electroactive interferents. Under optimized conditions, the method included a wide linear response range (0.05 to 120 ng mL −1 ) and a low detection limit of 8.0 fg mL −1 (S/ N  = 3). The synthesis of Ag-MOFs is relatively simple, and Ag-MOFs are not only used as nanocarriers for immobilizing anti-CEA but also acted as electroactive materials for a signal probe. The voltammetric immunoassay is stable, inexpensive, sensitive, and selective. Based on these advantages, the method holds great promise for applications in the point-of-care disease and environmental monitoring. Schematic presentation of a novel electrochemical immunoassay for the carcinoembryonic antigen (CEA) using silver metal-organic frameworks (Ag-MOFs) as a signal probe.

CAS / MDL: 308068-56-6
研究领域: 分析化学 · 生物化学 · 纳米技术 · 医学诊断
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MICROCHIMICA ACTA · 2022 ·Vol. 189 ·期 2 ·1-7 · IF 6.408

Photochromic immunoassay for tumor marker detection based on ZnO/AgI nanophotocatalyst

Zhang Bing,Wang Xue,Cheng Yan

A photochromic immunoassay was built for tumor marker detection based on ZnO/AgI nanophotocatalyst. Frist, ZnO/AgI nanoparticles were synthesized and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and Fourier transform infrared spectrometry (FTIR). The color development is caused by tetramethyl benzidine (TMB) solution oxidated by ZnO/AgI nanomaterials. The electron transitions in ZnO/AgI nanomaterials are driven by visible light irradiation, generating photogenerated hole and oxidizing TMB to blue solution. Appropriate band width between ZnO and AgI promotes separation of photogenerated electrons and holes and enhances oxidation efficiency. A sandwich-type immunoassay was constructed based on ZnO/AgI nanomaterial as labels. The absorbance at 650 nm of reaction solution is positively correlated with antigen concentration. The developed immunoassay showed good performance for carcinoma embryonic antigen (CEA) detection in the range 0.1–7.0 ng/mL with a detection limit of 65 pg/mL. The photochromic immunoassay also exhibited preferable selectivity, repeatability, and stability. Graphical abstract A novel colorimetric immunoassay was constructed based on ZnO/AgI photocatalyst. ZnO/AgI nanomaterials occur electron transitions under visible light irradiation and generate photogenerated hole, which can oxidize TMB to blue solution. Carcinoembryonic antigen in sample was detected sensitively due to the high catalytic efficiency of ZnO/AgI nanomaterials.

研究领域: 生物化学 · 纳米技术 · 分析化学 · 癌症研究
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

Patrinia villosa treat colorectal cancer by activating PI3K/Akt signaling pathway

Xiao-chen Li,Shuai Wang,Xin-xin Yang,Tian-jiao Li,Jia-xing Gu,Lin Zhao,Yong-rui Bao,Xian-sheng Meng

Ethnopharmacological relevance At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage to the body of the patient. Patrinia villosa Juss. (P.V), is a well-known traditional chinese medicine (TCM), and is recorded in the Compendium of Materia Medica as a necessary article for the treatment of intestinal carbuncle . It has been incorporated into traditional cancer treatment prescriptions in modern medicine. While the mechanism of action of P.V in the treatment of CRC remains unclear. Aim of the study: To investigate P.V in treating CRC and clarify the underlying mechanism. Materials and methods This study was based on Azoxymethane (AOM) combined with the Dextran Sulfate Sodium Salt (DSS)-induced CRC mouse model to clarify the pharmacological effects of P.V. The mechanism of action was found by metabolites and metabolomics. The rationality of metabolomics results was verified through the clinical target database of network pharmacology , and find the upstream and downstream target information of relevant action pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using quantitative PCR (q-PCR) and Western blot . Results The number and the diameter of tumors were decreased when mice were treated with P.V. P.V group section results showed newly generated cells which improved the degree of colon cell injury. Pathological indicators presented a trend of recovery to normal cells. Compared to the model group, P.V groups had significantly lower levels of the CRC biomarkers CEA, CA19-9, and CA72-4. Through the evaluation of metabolites and metabolomics, it was found that a total of 50 endogenous metabolites had significant changes. Most of these are modulated and recovered after P.V treatment. It alters glycerol phospholipid metabolites, which are closely related to PI3K target, suggesting that P.V can treat CRC though the PI3K target and PI3K/Akt signaling pathway. q-PCR and Western blot results also verified that the expression of VEGF, PI3K, Akt, P38, JNK, ERK1/2, TP53, IL-6, TNF- α and Caspase-3 were significantly decreased, whereas that of Caspase-9 was increased after treatment. Conclusion P.V is dependent on PI3K target and PI3K/Akt signaling pathway for CRC treatment.

CAS / MDL: 25843-45-2
研究领域: 肿瘤学 · 药理学 · 中医药 · 分子生物学
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Nanoscale · 2017 ·Vol. 9 ·期 47 ·18711-18722 · IF 7.367

Fluorescence quenching-based signal amplification on immunochromatography test strips for dual-mode sensing of two biomarkers of breast cancer

Bo Zhang,Wenjuan Ma,Fuxin Li,Weichen Gao,Qian Zhao,Weipan Peng,Jiafang Piao,Xiaoli Wu,Hanjie Wang,Xiaoqun Gong,Jin Chang

Recently, immunochromatography test strips (ICTS) have been fully developed for point-of-care testing (POCT). However, the intrinsic limitations including non-quantitative detection of colloidal gold ICTS and low sensitivity of fluorescence ICTS (FICTS) significantly restrict their further application in clinical diagnosis. Taking advantages of rapid colorimetric qualitative detection and fluorescence quantitation, we designed a kind of sensitive and dual-mode magnetic FICTS (mFICTS) based on PLGA@Fe3O4 super-paramagnetic nanosphere (SPMN) probes quenching multiplex fluorescer on the test line through sandwich immunoreactions. Owing to the large number of Fe3O4 nanoparticles (about 47) encapsulated in one SPMN, about 2680 Cy5 molecules were quenched by one SPMN on the test line such that to significantly improve the analytical sensitivity as well as the detection of whole blood samples via magnetic separation. Moreover, the aggregation of black SPMN on the test line enabled a quick naked-eye screening in 3 min. For high accuracy breast cancer diagnosis, combined determination of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA153) was performed on one mFICTS with the limits of detection of about 0.06 ng mL−1 and 0.09 U mL−1, respectively. Then, more than 50 clinical serum samples were investigated for high-resolution screening by mFICTS, and the results were coincident with those obtained by electrochemiluminescence immunoassay (ECLIA). Thus, the designed mFICTS is suitable for point-of-care diagnostics.

CAS / MDL: 57-50-1
研究领域: 生物医学工程 · 分析化学 · 临床诊断
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ANALYTICA CHIMICA ACTA · 2017 · IF 4.95

The label-free immunosensor based on rhodium@palladium nanodendrites/sulfo group functionalized multi-walled carbon nanotubes for the sensitive analysis of carcino embryonic antigen

Hui Lv,Yueyun Li,Xiaobo Zhang,Zengqiang Gao,Jinhui Feng,Ping Wang,Yunhui Dong

In this work, bimetallic core-shell rhodium@palladium nanodendrites (Rh@Pd NDs) loaded on sulfo group functionalized multi-walled carbon nanotubes (MWCNTs-SO 3 H) were combined to form Rh@Pd NDs/MWCNTs-SO 3 H nanocomposites. And the composites were used to construct a simple and label-free electrochemical immunosensor for carcino embryonic antigen (CEA) detection using differential pulse voltammetry (DPV). Rh@Pd NDs with dendritic nanostructure not only provide abundant catalytically active sites, but also increase the loading of antibody, which could improve the analytical performance and result in high sensitivity. In addition, the MWCNTs-SO 3 H could further enhance electrochemical properties due to the excellent conductivity, good solubility and high surface area. Taking advantages of both Rh@Pd NDs and MWCNTs-SO 3 H, the proposed immunosensor showed a broad linear range from 25 fg mL −1 to 100 ng mL −1 for CEA detection and a low detection limit of 8.3 fg mL −1 (signal-to-noise ratio of 3) under optimal experimental conditions. Moreover, the expected immunosensor exhibited good reproducibility and high sensitivity, which could achieve excellent analysis of CEA in human serum with satisfactory results. Therefore, the Rh@Pd NDs/MWCNTs-SO 3 H nanocomposites may be considered as a sensing platform for fabrication of simple, ultrasensitive and label-free electrochemical immunosensor.

CAS / MDL: 10049-07-7 13820-53-6
研究领域: 纳米技术 · 电化学 · 生物传感器 · 分析化学 · 癌症诊断
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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Click reaction-assisted construction of antifouling immunosensors for electrochemical detection of cancer biomarkers in human serum

Min Chen,Yang Li,Rui Han,Qiuji Chen,Lingyun Jiang,Xiliang Luo

Herein, an electrochemical immunosensor capable of detecting targets in human serum with ultralow fouling and high sensitivity was successfully constructed through a click reaction. One designed biotinylated peptide was associated with the other peptide functionalized with biotin and azide groups at its two terminals, to form a branched antifouling peptide through the streptavidin-biotin affinity interaction, and it was attached to the electrode to construct an antifouling interface. Then, the exposed azide group on the branched peptide was used to link the antibody modified with 5′-dibenzocyclooctyne (DBCO), and the immunosensor was thus constructed with the aid of the click reaction between the azide group and the DBCO. The developed antifouling immunosensor demonstrated a wide linear response range for carcinoembryonic antigen (CEA) and a low limit of detection of 40 fg mL −1 , which is much superior to the sensing performance of the immunosensor prepared through the normal EDC/NHS method. The immunosensor was capable of assaying CEA in undiluted serum samples with satisfying accuracy when compared with a clinically approved method. This work offered an effective strategy to develop various biosensors through the conjugation of antifouling peptides with different antibodies.

CAS / MDL: 126213-50-1 7791-03-9
研究领域: 分析化学 · 生物化学 · 生物传感器 · 电化学 · 癌症研究
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