ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Zhaoyan Tian,Li Mi,Yafeng Wu,Fengying Shao,Mingqiang Zou,Zhenxian Zhou,Songqin Liu
This work reports an electrofluorochromic strategy on the basis of electric field control of fluorescent signal generation on bipolar electrodes (BPEs) for visualizing cancer cell surface glycoprotein (mucin 1). The device included two separate cells: anodic sensing cell and cathodic reporting cell, which were connected by a screen-printing electrode patterned on poly(ethylene terephthalate) (PET) membrane. In the sensing cell, anti-MUC1 antibody immobilized on a chitosan-multiwalled carbon nanotube (CS-MWCNT)-modified anodic BPE channel was used for capturing mucin-1 (MUC1) or MCF-7 cancer cells. Then ferrocene (Fc)-labeled mucin 1 aptamers were introduced through hybridization. Under an applied voltage, the ferrocene was oxidized and the electroactive molecules of 1,4-benzoquinone (BQ) in the cathodic reporting cell were reduced according to electroneutrality. This produced a strongly basic 1,4-benzoquinone anion radical (BQ•–), which turned on the fluorescence of pH-responsive fluorescent molecules of (2-(2-(4-hydroxystyryl)-6-methyl-4H-pyran-4-ylidene)malononitrile) (SPM) coexisting in the cathode reporting cell for both spectrophotometric detection and imaging. This strategy allowed sensitive detection of MUC1 at a concentration down to 10 fM and was capable of detecting a minimum of three MCF-7 cells. Furthermore, the amount of MUC1 on MCF-7 cells was calculated to be 6.02 × 104 molecules/cell. Our strategy also had the advantages of high temporal and spatial resolution, short response time, and high luminous contrast and is of great significance for human health and the promotion of life science development.
研究领域:
生物化学
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生物医学工程
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分析化学
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癌症研究
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DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Xiaoming Su,Xinyu Liu,Yangcenzi Xie,Mingyang Chen,Chao Zheng,Hong Zhong,Ming Li
Protein profiles of exosomes (EXOs) in clinical samples of cancer patients have become a promising diagnostic and therapeutic biomarker. However, simultaneous quantitative analysis of multiple exosomal proteins of interest remains challenging. To address the unmet need, we develop a paper-based surface-enhanced Raman spectroscopy (SERS)-vertical flow biosensor, named iREX (integrated Raman spectroscopic EXO) biosensor, for multiplexed quantitative profiling of exosomal proteins in clinical serum samples of patients. Utilizing this iREX biosensor, we are able to quantitatively profile MUC1, HER2 and CEA in EXO samples derived from various breast cancer cell subtypes. The results show discriminative expression profiles of the three exosomal proteins in these cell subtypes, which allows for accurate diagnosis and molecular subtyping of breast cancer. We further validate the clinical utility of the iREX biosensor for simultaneous quantitative analysis of MUC1, HER2 and CEA in patient’s blood serums, thereby aiding in noninvasive breast cancer subtyping and longitudinal treatment monitoring. Our iREX biosensor integrating the SERS detection in a vertical flow diagnostic device offers great advantages of high sensitivity, molecular specificity, powerful multiplexing capability, and high diagnostic accuracy. We believe that the iREX biosensor could be a promising clinical tool for comprehensive analysis of exosomal proteins in clinical samples for personalized diagnosis and precise management of breast cancer.
研究领域:
生物医学工程
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肿瘤学
·
诊断学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
You Zhou,Kai Yang,Jian Wang,Ruijuan Guan,Wei Liu,Chaowei Wen,Liang Yuan,Tiange Zhang,Wei Feng,Yuanyuan Li,Jingyi Xu,Wenju Lu
Backgrounds: Exposure to fine particulate matter (PM2.5) triggers airway inflammation through the activation of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, contributing to the pathogenesis of various acute and chronic respiratory diseases. Mucin 1 (MUC1), a transmembrane glycoprotein highly expressed on airway epithelial cells, is known to modulate TLR-mediated inflammatory responses. However, the specific role and molecular mechanism by which MUC1 regulates PM2.5-induced airway inflammation remain inadequately understood.Methods: Lung injury models were established using Muc1+/+ and Muc1-/- rats via intranasal instillation of PM2.5. Histopathological changes and inflammatory responses were evaluated following treatment. In parallel, human bronchial epithelial cells (16HBE) were transfected with MUC1 overexpression and knockdown plasmids, along with corresponding controls. An IRAK4-specific inhibitor was employed to explore the mechanistic role of MUC1 in regulating the TLR4/IRAK4/NF-κB signaling cascade and associated pyroptosis.Results: PM2.5 exposure caused notable epithelial disruption, inflammatory infiltration, and submucosal fibrosis in Muc1-/- rats compared to Muc1+/+ controls. While TLR4 expression was not significantly altered, NF-κB and NLRP3 inflammasome activity were markedly elevated in Muc1-deficient rats. In 16HBE cells, MUC1 overexpression attenuated, whereas MUC1 knockdown exacerbated, PM2.5-induced activation of the IRAK4/NF-κB signaling axis and pyroptosis-related markers (IL-1β, IL-18, NLRP3, GSDMD). Furthermore, pharmacological inhibition of IRAK4 mitigated these effects, confirming the involvement of the IRAK4 pathway in MUC1-mediated protection.Conclusions: MUC1 is upregulated in airway epithelial cells upon PM2.5 exposure and serves as a key endogenous inhibitor of airway inflammation. It exerts its anti-inflammatory and anti-pyroptotic effects by suppressing IRAK4 phosphorylation, thereby modulating downstream NF-κB/NLRP3/GSDMD signaling. These findings highlight MUC1 as a potential therapeutic target for PM2.5-induced airway inflammatory diseases.
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DOI
PubMed
高影响因子
ANALYST
·
2019
·Vol. 145
·期 1
·107-114
·
IF 4.019
Yu Zhou,Huiying Xu,Hua Wang,Bang-Ce Ye
Exosomes are membrane-enclosed phospholipid extracellular vesicles with a variety of tumor antigens which can be applied in the diagnosis and treatment of cancer due to the high secretion on the surface of cancer cells. Until now, many research studies on exosomes have been reported, but convenient and low-cost detection methods still need to be developed. Recently, we have developed a sensitive, simple and low-cost colorimetric aptasensor by designing a hairpin-like structure, which combined the highly specific MUC1 aptamer with a hemin/G-quadruplex for the detection of breast cancer exosomes. The hemin/G-quadruplex toward H2O2 reduction was used to generate an evidently strong colorimetric response owing to acting as a HRP-mimicking DNAzyme. The aptasensor is regarded as an “on–off” type switch, which strictly controls the process of reaction responding to the existence or not of exosomes. In our study, associated exosome detection limits are 3.94 × 105 particles per mL, which showed a higher sensitivity compared to commercial ELISA. Our method not only exhibited the advantages of being convenient and time-saving, with few instruments used, but also the signal generated using this method can be easily observed by the naked eye. Furthermore, the proposed strategy can well differentiate breast cancer patients from healthy individuals, demonstrating potential application in the analysis of clinical specimens.
研究领域:
癌症生物学
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分析化学
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生物技术
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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 Natural Medicines
·
2023
·
IF 3.3
He Dongjie,Song Yanli,Xiao Huidongzi,Shi Shaoqi,Song Hongyan,Cui Tianwei,Ni Tingting,Wang Jing,Ren Xingxing,Wei Aiwu
Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.
研究领域:
药理学
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生殖生物学
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分子生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Nianzu Liu,Jingyao Song,Yanwei Lu,Jason J. Davis,Fengxian Gao,Xiliang Luo
The rapid, convenient, and selective assaying of clinical targets directly in complex biological media brings with it the potential to revolutionize diagnostics. One major hurdle to impact is retention of selectivity and a tight control of nonspecific surface interactions or biofouling. We report herein, the construction of an antifouling interface through the covalent attachment of designed branched zwitterionic peptides onto electrodeposited polyaniline film. The antifouling capability of the designed branched peptide significantly outperforms that of the commonly used PEG and linear peptides. The interfaces modified with branched peptides are exceptionally effective in reducing a nonspecific protein and cell adsorption, as verified by electrochemical and fluorescent characterization. The derived sensors with mucin1 protein (MUC1) aptamer as the recognition element detect MUC1-positive MCF-7 breast cancer cells in human serum with high sensitivity and selectivity. The linear response range of the cytosensor for the MCF-7 cell is from 50 to 106 cells/mL, with a limit of detection as low as 20 cells/mL. More importantly, the assaying performances remain unchanged in human serum owing to the presence of branched antifouling peptide, indicating feasibility of the cytosensor for practical cancer cell quantification in complex samples.
研究领域:
生物传感器
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癌症诊断
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材料科学
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分析化学
·
生物医学工程
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
·
IF 10.257
Juan Cai,Huawei Shen,Yonghong Wang,Yang Peng,Sitian Tang,Yalin Zhu,Qian Liu,Baiying Li,Guoming Xie,Wenli Feng
Accurate detection of circulating tumor cells (CTCs) has a pivotal role in the metastasis monitoring and prognosis of tumor. In this work, an ultrasensitive electrochemical cytosensor was developed based on excellent electrocatalytic materials and a dual recognition strategy. Herein, novel branched PtAuRh trimetallic nanospheres (b-PtAuRh TNS) were synthesized for the first time by a facile one-pot method, which had a huge specific surface area and outstanding catalytic activity. B-PtAuRh TNS linked with aptamers targeting mucin1 (MUC1) were served as signal tags to amplify the signal. As electrode modified material, the nanocomposites of Cabot carbon black (BP2000) and AuNPs were used to improve the electron transfer efficiency of electrode. In addition to using b-PtAuRh TNS labeled anti-MUC1 aptamers as signal probes, anti-EpCAM antibodies were worked as capture probes to achieve dual recognition of target cells. In other words, only cells expressing both MUC1 and EpCAM could produce electrochemical signal. The constructed cytosensor presented a wide linear range (5 - 1 × 10 6 cells mL −1 ) and a low detection limit (1 cell mL −1 ). It was worth noting that the proposed cytosensor could detect CTCs in clinical blood samples. To sum up, the developed cytosensor might become a promising detection platform for cancer diagnosis and tumor metastasis.
研究领域:
生物医学工程
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纳米技术
·
癌症研究
·
电化学
·
生物传感器
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
Xiaoting Li,Beibei Chen,Man He,Han Wang,Guangyang Xiao,Bin Yang,Bin Hu
In this work, we demonstrate a novel method based on inductively coupled plasma mass spectrometry (ICP-MS) detection with gold nanoparticles (Au NPs) and quantum dots (QDs) labeling for the simultaneous counting of two circulating tumor cell lines (MCF-7 and HepG2 cells) in human blood . MCF-7 and HepG2 cells were captured by magnetic beads coupled with anti-EpCAM and then specifically labeled by CdSe QDs-anti-ASGPR and Au NPs-anti-MUC1, respectively, which were used as signal probes for ICP-MS measurement. Under the optimal experimental conditions, the limits of detection of 50 MCF-7, 89 HepG2 cells and the linear ranges of 200-40000 MCF-7, 300-30000 HepG2 cells were obtained, and the relative standard deviations for seven replicate detections of 800 MCF-7 and HepG2 cells were 4.6% and 5.7%, respectively. This method has the advantages of high sensitivity, low sample consumption, wide linear range and can be extended to the simultaneous detection of multiple CTC lines in human peripheral blood.
研究领域:
分析化学
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癌症研究
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纳米技术
·
生物医学工程
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 8
·期 20
·1900791
·
IF 6.27
Junjie Liu,Yiwen Zhang,Wei Liu,Kaixiang Zhang,Jinjin Shi,Zhenzhong Zhang
Photodynamic therapy (PDT) is a noninvasive powerful tool for tumor treatment. However, phototoxicity seriously limits the clinical application of PDT, and activated PDT specifically response to tumor cell antigen is rarely reported. Herein, a tumor cell specific “switch-on” PDT nanoplatform, which employs a well-designed hairpin structure mucl protein (MUC1) aptamer (Apt) as specific linker to conjugate gold nanorod and Chlorin e6 (Ce6) (GNR/Apt-Ce6) is prepared, and “switch on” via conformational changes of aptamer-induced fluorescence resonance energy transfer missing between GNR and Ce6 for selective tumor therapy. In the absence of tumor cells, MUC1 Apt keeps a hairpin structure, leading to Ce6 closely adhered to the surface of GNR, PDT is in an “off” state even under the irradiations. On the contrary, in the presence of tumor cells with overexpressed MUC1, Apt specifically recognizes and binds to MUC1, resulting in conformational changes of Apt from regular hairpin to extended chain structure. Thus with an enlarged distance between Ce6 and GNR, PDT is switched-on. GNR/Apt-Ce6 shows excellent PDT efficacy in tumor-bearing mice (55.1% vs 1.3%, tumor apoptosis rate of GNR/Apt-Ce6 vs GNR/random sequence-Ce6) due to its high tumor-targeting and “switch-on” properties. The strategy of tumor antigen activated PDT is expected to provide a new perspective for clinical application.
研究领域:
癌症生物学
·
纳米技术
·
治疗学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Wenyue Zhang,Ziyi Li,Xiaoli Lun,Yingshu Guo
Targeting tumor markers is one of the most important approaches to tumor therapy, and the “suicide” pattern of tumor marker response is a very challenging study. Telomerase, as one of the key factors associated with human longevity and cancer progression, is considered to be an emerging biomarker for cancer diagnosis. The targeted drug delivery nanobomb─BIBR1532@HSN/FQDNA/MUC1 aptamer (B@HDA) is prepared in this study based on hollow silica nanoparticles (HSN) and CRISPR systems. Amino-modified FQDNA and amino-modified MUC1 aptamer are covalently attached to the surface of carboxyl-functionalized HSN. The modified MUC1 aptamer directs the nanobomb to specifically target breast cancer cells (MCF-7) and FQDNA sequesters the telomerase inhibitor (BIBR1532) within the HSN. Telomerase primers (TPs) is recognized by the highly expressed telomerase in MCF-7 cells and is elongated to form DNA substrates. The substrate pairs with crRNA bases to effectively activate CRISPR-Cas12a. The activated CRISPR-Cas12a precisely cut FQDNA, releasing BIBR1532, which inhibits telomerase activity. This strategy achieves telomerase “suicide”. The nanobomb described above has the following advantages. (1) The “closing” effect of FQDNA contributes to reducing the nonspecific release of BIBR1532. (2) B@HDA, combined with CRISPR, regulates mitochondrial dysfunction and cell senescence in MCF-7 cells. (3) In the tumor-bearing mouse model, B@HDA, combined with CRISPR, exhibits good biocompatibility and an obvious tumor ablation effect on MCF-7 tumors, suggesting potential application prospects across a wide range of cancer cell lines. In summary, the proposed nanobomb provides a tunable switch approach for the specific inhibition of telomerase and the reduction of tumor cell growth, representing a promising avenue for promoting senescence and treating cancer.
研究领域:
癌症研究
·
分子生物学
·
纳米技术
·
基因工程
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2023
·
IF 4.4
Xinpeng Zhang,Xinyu Li,Danfeng Wang,Tianxin Weng,Lu Wang,Lixia Yuan,Qingpeng Wang,Jie Liu,Yushu Wu,Min Liu
Chemotherapy–phototherapy (CTPT) combination drugs co-loaded by targeted DNA nanostructures can achieve controlled drug delivery, reduce toxic side effects and overcome multidrug resistance. Herein, we constructed and characterized a DNA tetrahedral nanostructure (MUC1-TD) linked with the targeting aptamer MUC1. The interaction of daunorubicin (DAU)/acridine orange (AO) alone and in combination with MUC1-TD and the influence of the interaction on the cytotoxicity of the drugs were evaluated. Potassium ferrocyanide quenching analysis and DNA melting temperature assays were used to demonstrate the intercalative binding of DAU/AO to MUC1-TD. The interactions of DAU and/or AO with MUC1-TD were analyzed by fluorescence spectroscopy and differential scanning calorimetry. The number of binding sites, binding constant, entropy and enthalpy changes of the binding process were obtained. The binding strength and binding sites of DAU were higher than those of AO. The presence of AO in the ternary system weakened the binding of DAU to MUC1-TD. In vitro cytotoxicity studies demonstrated that the loading of MUC1-TD augmented the inhibitory effects of DAU and AO and the synergistic cytotoxic effects of DAU + AO on MCF-7 cells and MCF-7/ADR cells. Cell uptake studies showed that the loading of MUC1-TD was beneficial in promoting the apoptosis of MCF-7/ADR cells due to its enhanced targeting to the nucleus. This study has important guiding significance for the combined application of DAU and AO co-loaded by DNA nanostructures to overcome multidrug resistance.
研究领域:
纳米技术
·
药学
·
癌症研究
·
分子生物学
·
生物物理学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 16
·11215-11224
·
IF 3.9
Haidi Feng,Lu Zhao,Zhiqiang Bai,Zhihui Xin,Chaoyu Wang,Lizhen Liu,Jinping Song,Haifei Zhang,Yunfeng Bai,Feng Feng
Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
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