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
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癌症研究
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电化学
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生物传感器
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2018
·
IF 6.042
Yanyan Yu,Yuan Yang,Jinhua Ding,Si Meng,Chenglin Li,Xiaoxing Yin
Circulating tumor cells (CTCs) served as an important biomarker for tumor recurrence and prediction of prognosis. However, selective capture and quantification of CTCs from whole blood was still full of challenge due to the extremely scare number of CTCs. Moreover, how to keep a high cell viability after capture remained to be solved. Here, we described a ratiometric fluorescent probe for the efficient capture and accurate determination of CTCs by conjugating graphitic carbon nitride quantum dots (g-CNQDs) with gold nanoclusters (AuNCs) and further linking with anti-EpCAM antibody to acquire the CTC-specific immune probe. In this probe, AuNCs protected by albumin V bovine played the role as the fluorophore reference and anti-EpCAM-attached g-CNQDs acted as both the response signal and specific recognition element for sensing CTCs. In the presence of CTCs, the quenched fluorescence of the immune probe at 500 nm was recovered due to the detachment of anti-EpCAM from the probe, whereas the intensity at 650 nm was essentially unchanged. This strategy realized the highly sensitive detection of CTCs in whole blood down to one CTC. Furthermore, it was demonstrated that the designed probe allowed capturing living CTCs with minimal cell damage. The subsequent reculture of captured cells for proliferation revealed that after a 7 day proliferation, almost 28 MCF-7 cells were obtained from one target cell. The immune probe was successfully applied into capture and detection of CTCs from clinical cancer patients. Our data suggested the good potential of fluorescent probe for the clinical diagnosis of cancers.
研究领域:
生物医学工程
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纳米技术
·
癌症生物学
·
分子诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Yuping Liu,Beibei Zhang,Xueyuan Wu,Fan Wang,Zhiyi Yang,Mengyi Li,Kaixuan Sheng,Yue Yan,Liang Zhu,Hui Jing,Yanmin Wu,Lili Hu,Yanyan Yu,Chenglin Li
Programmed cell death 1 ligand 1 (PD-L1) immunotherapy holds a pivotal role in lung cancer treatment. However, current methods for monitoring PD-L1 expression exhibit several limitations, including hysteresis and the invasive nature of tissue sampling. Circulating tumor cells (CTCs), the important biomarkers in liquid biopsy, are minimally invasive and facilitate continuous monitoring. Consequently, integrating CTC counting with PD-L1 expression analysis offers more comprehensive insights for the development of personalized treatment strategies development and efficacy evaluations. In this study, we presented a facile liquid biopsy assay designed for the dynamic monitoring of PD-L1 expression on CTCs captured from non-small cell lung cancer (NSCLC) patients. This assay was achieved by fabricating two high-performance probes: EpCAM and Vimentin dual-aptamer modified nitrogen-doped carbon quantum dots probe (E/V-apt-N-CQDs) and hairpin PD-L1 aptamer coupled with gold nanoparticles (PD-L1-apt-AuNPs). The E/V-apt-N-CQDs probe effectively captured two types of CTC models (H1299 and A549) exhibiting differential PD-L1 expression. Additionally, reagent-less detection of PD-L1 levels on CTCs was achieved using a portable magnetic electrochemical sensor with excellent specificity and sensitivity, which was capable of measuring PD-L1 concentrations as low as 2 ng/mL. Finally, this assay was applied in 41 NSCLC patients to investigate the correlation between CTC numbers or PD-L1 expression and disease progression and immunotherapy efficacy. The results indicated a significant association between elevated CTC counts or reduced PD-L1 levels and clinical progression. Moreover, this liquid assay successfully monitored dynamic changes in CTCs and PD-L1 expression in NSCLC patients receiving immunotherapy, indicating its potential for clinical application.
研究领域:
医学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 17
·5624-5640
·
IF 7.367
Yu Gao,Xiaodong Xie,Fengqiao Li,Yusheng Lu,Tao Li,Shu Lian,Yingying Zhang,Huijuan Zhang,Hao Mei,Lee Jia
Rare circulating tumor cells (CTCs) cause >50% of primary colorectal cancer survivors to develop deadly metastasis at 3–5 years after surgery; the current chemotherapies can do nothing about these cells. Herein, we synthesized a novel doxorubicin (DOX)-entrapped mesoporous silica nanoparticle (MSN), covalently-conjugated with two aptamers, for simultaneously targeting EpCAM and CD44, the typical surface biomarkers of colorectal CTCs. The nanomissile can specifically capture the metastasis-prone CTCs spiked in healthy human blood in a competitive-binding manner. The binding not only accurately delivers DOX into the cancer cells via the biomarker-mediated endocytosis to inhibit CTC viability through the DOX-dependent mechanism, but also inhibits the adhesion of cancer cells to the endothelium and the consequent transmembrane migration through the DOX-independent mechanism. The molecular entity of the conjugate and its pharmaceutical DOX encapsulation-releasing capacity are well-demonstrated via various physiochemical characterizations including gel electrophoresis, which proves the >8-hour biostability of the nanomissile in blood, long enough for it to chase CTCs in mice and synergistically inhibit the CTC-induced lung metastasis more potently than its single aptamer-conjugated counterparts and DOX itself. The present strategy may pave a new avenue for safe and effective cancer metastasis chemoprevention.
研究领域:
纳米技术
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癌症研究
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药学科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
·
IF 10.257
Liang Zhu,Xingqing Feng,Shenhao Yang,Jianyun Wang,Yixin Pan,Jinhua Ding,Chenglin Li,Xiaoxing Yin,Yanyan Yu
The number of CTCs in peripheral blood is of great significance for the early diagnosis, recurrence and prognosis evaluation of tumor patients. Consequently, it is required to develop simple and effective technique to realize the capture and detection of rare number CTCs. Herein, a SiO 2 , gelatin and biotinylated EpCAM aptamer P1 modified Fe 3 O 4 immunomagnetic nanoparticles (IMNs) were prepared for the specific capture and nondestructive release of trace amounts of CTCs. Then, utilizing the peroxidase-like activity of single-walled carbon nanotubes (SWCNTs) and the effect of non-specific DNA sequences on this activity, a colorimetric probe was constructed by modifying the three DNA sequences (mDNA) onto the IMNs. When target cell was present, due to the specific interaction between cells and P1, the conformational structure of P1 was changed. Consequently, the mDNA linked with P1 on IMNs was replaced by the cell and released from IMNs. In this way, the quantification of captured CTCs could be converted to that of released mDNA. This strategy combined the capture and detection of CTCs as a whole and could detect down to 10 cells with a high selectivity . Finally, we achieved the accurate quantification of CTCs in lysed bloods from 12 clinical tumor patients, which exhibited a great promise for further clinical applications.
研究领域:
生物技术
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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
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临床化学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 7
·1812-1820
·
IF 7.59
Yanping Xu,Dinghu Zhang,Jie Lin,Xiaoxia Wu,Xiawei Xu,Ozioma Udochukwu Akakuru,Hao Zhang,Zhewei Zhang,Yujiao Xie,Aiguo Wu,Guoliang Shao
Circulating tumor cells (CTCs) usually shed from primary and metastatic tumors serve as an important tumor marker, and easily cause fatal distant metastasis in cancer patients. Accurately and effectively detecting CTCs in a peripheral blood sample is of great significance in early tumor diagnosis, efficacy evaluation, and postoperative condition monitoring. In this work, a TiO2@Ag nanostructure is structured as a SERS substrate, rhodamine 6G (R6G) is used as a Raman signal molecule, the reduced bovine serum protein (rBSA) acts as a protective agent, and folic acid (FA) acts as a target molecule to specifically recognize cancer cells. A TiO2@Ag-based SERS bioprobe is successfully prepared with the feature of ultrahigh sensitivity, good specificity, low toxicity, and high accuracy in CTC detection. The remarkable SERS activity of the TiO2@Ag nanostructure is synergistically contributed by surface plasmon resonance and photon-induced charge transfer mechanism. The limit of detection for rhodamine 6G (R6G) molecules adsorbed on the TiO2@Ag SERS substrate is 5 × 10−14 M, and the corresponding SERS enhancement factor can reach 7.61 × 107. The designed TiO2@Ag–R6G–rBSA–FA SERS bioprobe is effectively utilized in detecting various cancer cells in rabbit blood, and the limit of detection (LOD) for the target cancer cell is 1 cell per mL. Notably, CTCs in peripheral blood of six clinical liver cancer patients are successfully recognized via the TiO2@Ag-based SERS bioprobe. Accurately recognizing CTCs in peripheral blood based on the TiO2@Ag–R6G–rBSA–FA SERS bioprobe is also carefully verified by in situ immunofluorescence staining experiments, which directly supports the CTC detection accuracy of the SERS strategy. These results demonstrate that the TiO2@Ag-based SERS bioprobe has great application potential in early screening and diagnosis of tumors.
研究领域:
生物医学工程
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纳米技术
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癌症生物学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Kemeng Zhang,Jiajun Li,Ye Li,Wen Zhang,Guohai Liang,Tao Zhang
Detection of circulating tumor cells (CTCs) has proven to be a crucial approach for early diagnosis, prognosis, and monitoring of cancer treatment. However, due to the low abundance of CTCs in blood, achieving accurate detection in the presence of a large number of blood cells remains challenging. In this study, we present a novel self-catalytic nanomachine for quantitative detection of CTCs, which includes a dual aptamer-triggered Catalytic Hairpin Assembly (CHA) reaction and subsequent UCNP-DNA-based biosensing. The dual-aptamer recognition, the two-step CHA reaction and the UCNP ratiometric sensing luminescence provide the assay with high specificity and sensitivity. Using MDA-MB-231 cells as model targets, the proposed detection system affords a wide linear detection range and a detection limit as low as 3 cells. Our system offers sensitive detection of CTCs without the need for enzymatic involvement, indicating its substantial potential for early cancer diagnosis and treatment based on CTCs.
研究领域:
生物医学工程
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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
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Min Fan,Zongyang Yu,Kan Luo,Ping Chen,Duo Lin,Yating Lin,Xueliang Lin,Jingbo Chen,Shangyuan Feng
Tumor heterogeneity and drug resistance remain major obstacles to the implementation of personalized therapeutic strategies in lung cancer. Circulating tumor cell (CTC)-based liquid biopsy provides a powerful, minimally invasive tool for tracking dynamic changes in tumor heterogeneity and elucidating mechanisms of treatment response and drug resistance. Herein, we present a portable, field-deployable surface-enhanced Raman scattering (SERS) immunoprobe platform capable of multiplexed detection of CTC membrane biomarkers to monitor tumor heterogeneity throughout the course of therapy. Utilizing a cocktail of multicolor-encoded immunoprobes, the platform achieves single-cell phenotypic resolution via antigen-specific spectral fingerprinting, validated by flow cytometry. It demonstrates ultra-sensitive CTC quantification (limit of detection of 1.7 cells/mL) and precise molecular subtyping across four cell lines (HCC827, A549, BEAS-2B, and HeLa). Integrated with orthogonal partial least squares discriminant analysis (OPLS-DA), the platform accurately distinguishes clinically relevant cell types with 99% classification accuracy, successfully stratifying metastatic versus non-metastatic lung cancer ( n = 24) and capturing treatment-driven CTC evolution in longitudinal studies ( n = 7). Our results highlight a transformative strategy for real-time interception of drug resistance trajectories, positioning dynamic CTC phenotyping as a critical tool for adaptive therapy and prognostic assessment in precision oncology.
研究领域:
肿瘤学
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生物医学工程
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分子诊断
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纳米技术
·
精准医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LAB ON A CHIP
·
2021
·Vol. 21
·期 20
·3888-3898
·
IF 6.799
Rongke Gao,Changbiao Zhan,Chunyu Wu,Yang Lu,Baoqiang Cao,Jing Huang,Feng Wang,Liandong Yu
Hepatocellular carcinoma (HCC) is a harmful malady that truly debilitates human health, and hence it is of significance to isolate and on-line profile the phenotype of HCC cells for further diagnosis and therapy. We developed a novel strategy for efficient capture and in situ heterogeneous phenotype analysis of circulating tumor cells (CTCs) at the single-cell level based on surface-enhanced Raman scattering (SERS) fingerprint characteristics. Herein, a new microfluidic chip with lantern-like bypass structure was designed to capture CTCs by their large size from whole blood. Furthermore, two types of SERS-aptamer nanotags were fabricated, realizing spectral recognition of single CTCs in accordance with the surface membrane protein expression. Up to 84% of CTCs with a purity of 95% were captured from whole blood samples using the present SERS-aptamer based microfluidic chip at 20 μL min−1. The results showed that the proposed strategy can successfully identify HCC cell subtypes by SERS measurements, which was related to the clinical surface biomarkers. This may open a new avenue for serving as a powerful tool of cancer diagnosis and prognosis evaluation.
研究领域:
癌症生物学
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生物医学工程
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2025
·
IF 4.3
Jianwei Dong,Huan Wang,Jiaxing Huang,Hao He,Zhihai Wei,Weixuan Bai,Jingzhang Geng,Cong Min
Circulating tumor cells (CTCs) may be overlooked by detection techniques based on epithelial cell adhesion molecules (EpCAM) because of epithelial- mesenchymal transition (EMT). This work established an efficient microfluidic magnetic cell immunoassay (E- μ MCI) for CTCs via folate-modified magnetic beads (MBs@FA). Upon capture by MBs@FA, MCF-7 (EpCAM + Vimentin − ) and MDA-MB-231 (EpCAM − Vimentin + ) were labeled with horseradish peroxidase (HRP) and alkaline phosphatase (AP) via anti-EpCAM and anti-Vimentin, respectively. These labeled target cells were then concentrated in a microchannel’s tiny space. These phenotypes were recognized by fluorescent substances generated by HRP and AP, and cell quantity was determined via the growth rate of fluorescent products. MBs@FA’s efficient capture and microchannel’s signal amplification enabled ultrasensitive CTCs detection via E- μ MCI, with the detection limits of 1.8 and 2.8 cells/mL for MCF-7 and MDA-MB-231, respectively. This method also exhibited excellent selectivity and repeatability, achieving acceptable recovery and stability in actual sample determination. More remarkably, within the EMT model of CTCs, the recovery rate of E- μ MCI was observed to range from 94.3 % to 102.8 %. It was far greater than the EpCAM-based approach, indicating that E- μ MCI has the potential to address CTC detection oversights and offer technical methodologies for studying the relationship between CTCs and cancer progression.
研究领域:
医学
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2018
·
IF 5.123
Yanyan Yu,Yuan Yang,Fan Wang,Jinhua Ding,Si Meng,Chenglin Li,Daoquan Tang,Xiaoxing Yin
This work demonstrated an effective strategy for the capture, identification and determination of multiple types of circulating tumor cells (CTCs) on functional and biocompatible immunomagnetic nanosphere interfaces (IMNs). The IMNs were achieved by functionalizing superparamagnetic iron oxide nanospheres (Fe 3 O 4 ) with polymerized ionic liquid (PIL), and then coating with epithelial-cell-adhesion-molecule antibody (anti-EpCAM). The IMNs exhibited outstanding cell capture efficiency (above 95%) and specificity when employed to separate multiple EpCAM-positive tumor cells, due to the abundant carboxyl groups in the structure of PIL, which enhanced the coupling efficiency of MNs with anti-EpCAM by chemical bonding between carboxyls and amines, thereby enabling more target cells adhered onto IMNs. Under the optimized capture conditions, IMNs were shown an excellent cell capture performance in the range of 5–400 cells/mL in three different cases (e.g., PBS, MCF-7 and THP-1 mixed cell suspension, lysed blood). More significantly, our results indicated that with modification of PIL, in addition to the capture efficiency, the cell viability rate of CTCs was also greatly improved (98%) owing to the nontoxic and biocompatible properties of PIL, which realized the proliferation of the rare number CTCs for further molecular characterization. Finally, the IMNs were successfully applied to the isolation and detection of CTCs in cancer patient peripheral blood samples and as low as one CTC in the whole blood was captured and identified by the ICC method.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2023
·
IF 4
Yu Li,Ting Zhang,Jing Huang,Haiyan Dong,Jingjing Xie,Lee Jia
Background/Objective Circulating tumor cells (CTCs) are known as the root of cancer metastasis. Capture and inhibition of CTCs may prevent metastasis. Due to the rarity of CTCs in vivo, the current technology about CTCs capture is still challenging. The aim of our study was to conjugate the enhanced biostable double-strand (ds) circular aptamer (dApR) with dendrimers for capturing and restraining CTCs in vitro and in vivo.Methods CEM-targeting aptamer (Ap) was looped by ligation after phosphorylation to form circular ds aptamer dApR, which was then conjugated to dendrimers by biotin-streptavidin affinity reaction and named as G-dApR. The physicochemical properties of G-dApR were characterized by using PAGE gel electrophoresis, UV, DLS, AFM, fluorophotometer and laser confocal microscope. Biostability of G-dApR was also analyzed by gel electrophoresis. Confocal microscopy and flow cytometry were then performed to determine the binding specificity of G-dApR to CEM cells and the captured CTCs in mice and in human blood. Apoptosis of the captured cells was finally evaluated by using MTT assay, DAPI staining, AO/EB staining, cell cycle analysis and Annexin V-FITC/PI staining.Results Physicochemical characterization demonstrated the entity of dApR and G-dApR, and the nano-size of G-dApR (about 180 nm in aqueous phase). G-dApR exhibited the excellent biostability that confers their resistance to nuclease-mediated biodegradation in serum for at least 6 days. In our established CTCs model, we found that G-dApR could specifically and sensitively capture CTCs not non-target cells even in the presence of millions of interfering cells (108), in mice and in human blood. Finally, the activity of captured CTCs was significantly down-regulated by G-dApR, resulting in apoptosis.Conclusion We created the enhanced biostable dApR-coated dendrimers (G-dApR) that could specifically capture and restrain CTCs in vitro and in vivo for preventing CTC-mediated cancer metastasis.
研究领域:
肿瘤学
·
分子生物学
·
纳米技术
·
生物医学工程
✓ 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）