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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

Optimized multifunctional peptide based magnetic biointerface for selective capture and sensitive detection of circulating tumor cells in breast cancer

Rong Qin,Mengqi Bai,Feiyi Zhang,Zengkai Wang,Fenglian Liu,Mingdong Dong,Lei Liu,Jian Xu

The detection of circulating tumor cells (CTCs) has emerged as a promising approach for the early diagnosis, therapeutic monitoring, and prognosis of malignant tumors. In this study, we present a novel magnetic nanoparticle (MP) functionalized with dual recognition peptides targeting the epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor 2 (HER2). Additionally, bovine serum albumin (BSA), an anti-fouling agent, is employed onto MP, effectively preventing the non-specific adhesion of platelets and proteins. This multifunctional peptide based magnetic biointerface (MPMB) platform effectively captures breast cancer cells in model systems and isolates CTCs from the blood of breast cancer patients. CTC enumeration of peripheral blood samples from 40 breast cancer patients, 30 benign breast tumor patients, and 30 healthy donors revealed a 70 % positivity rate in breast cancer patients (28/40), 6.7 % in benign breast tumor patients (2/30), and no positivity in healthy donors (0/30). CTC counts were significantly higher in breast cancer patients with advanced stages, particularly in those with distant metastasis, compared to early-stage patients ( p  < 0.05). Moreover, among 10 breast cancer patients with positive CTC detection prior to surgery, 6 showed negative CTC results post-surgery. These findings indicate that the MPMB approach provides a simple, flexible, and efficient platform for monitoring therapeutic efficacy and evaluating prognosis in breast cancer patients undergoing treatment.

CAS / MDL: 62-31-7 9048-46-8
研究领域: 医学 · 生物技术
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BIOLOGICAL TRACE ELEMENT RESEARCH · 2020 ·Vol. 198 ·期 1 ·58-67 · IF 2.639

Correlations between 13 Trace Elements and Circulating Tumor Cells in Patients with Colorectal Cancer in Guangzhou, China

Wang Hetao,Liu Hao,Zhou Meijuan,Shi Hanping,Shen Mei

We established a method of determining 13 trace elements (TEs) in whole blood, determined the levels of the TEs in patients with colorectal cancer (CRC), and examined the correlations between the TEs and circulating tumor cells (CTCs). A total of 93 CRC patients and 48 control subjects in Guangzhou, China, were included. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the blood levels of 13 TEs. CTCs of 13 CRC patients were examined using CanPatrol™. The levels of Mg, Fe, Zn, Se, Sr, Mo, and Ba in CRC patients were lower than those in control subjects (all, P  < 0.05). The levels of Mg, Fe, Zn, Se, and Ba decreased with increasing TNM stage. The reductions of Zn and Se levels were higher in early-stage than late-stage CRC patients. The levels of Cu and Ni were higher in CRC patients than in control subjects (both, P  < 0.05). The Cu level increased with increased TNM stage, and Ni level was higher in early-stage CRC patients as compared with late-stage CRC patients. Consequently, the TE levels showed differences as the process of TNM stage of CRC patients. There were correlations between the amount of CTCs and epithelial-CTCs (E-CTCs) and interstitial-CTCs (M-CTCs) ( P  < 0.05). The levels of Mg, Cr, Fe, Cu, Zn, Se, Sr, and Ba were correlated with the number of CTCs ( P  < 0.05). Specific TE patterns in whole blood may assist in the early diagnosis of CRC. The combined determination of TE levels and CTCs may be useful as an adjunct to staging and guiding treatments.

CAS / MDL: 9002-93-1
研究领域: 医学 · 肿瘤学 · 临床检验
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BIOMATERIALS · 2020 · IF 10.317

Hydrogen peroxide-response nanoprobe for CD44-targeted circulating tumor cell detection and H2O2 analysis

Chunting Li,Jiexuan Wang,Xinmiao Lu,Huang Ge,Xin Jin,Qinhua Guan,Yue su,Ruijun Pan,Peiyong Li,Wei Cai,Xinyuan Zhu

Circulating tumor cells (CTCs) represent the most common way of tumor metastasis and has been considered as a significant index for tumor diagnosis, staging and prognosis. However, CTC detection and analysis are always limited by the scarcity of CTC in the peripheral blood and the interference of blood cells. Therefore, here we presented with a hydrogen peroxide (H 2 O 2 )–response nanoprobes with CD44-targeted ability to reduce the interference of blood cells and improve the detection efficiency and accuracy and the pancreatic cancer cell was used to evaluate the feasibility of our probe. Shortly, hydrophobic H 2 O 2 -response naphthalimide-borate fluorophore was introduced onto the hydrophilic hyaluronic acid to form an amphiphilic complex, which could self-assemble into fluorescent nanoprobes in water. Our studies demonstrated that the nanoprobes were not only able to specifically recognize the pancreatic cancer cells with overexpressed CD44 proteins and reduce the influence of white blood cells in the peripheral blood, but also capable of semi-quantifying H 2 O 2 content in CTCs, Which could be further used as a significant index for tumor clinical evaluation and therapy.

研究领域: 肿瘤学 · 医学诊断 · 生物化学
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 20 ·3808-3816 · IF 7.571

A TiO2-based bioprobe enabling excellent SERS activity in the detection of diverse circulating tumor cells

Yanping Xu,Jie Lin,Xiaoxia Wu,Xiawei Xu,Dinghu Zhang,Yujiao Xie,Ting Pan,Yiwei He,Aiguo Wu,Guoliang Shao

Circulating tumor cells (CTCs) can be the seeds of tumor metastasis and are closely linked to cancer-related death. Fast and effective detection of CTCs is important for the early diagnosis of cancer and the evaluation of micrometastasis. However, the extreme rarity and heterogeneity of CTCs in peripheral blood make sensitive detection of CTCs a big challenge. In this paper, a TiO2-based surface-enhanced Raman scattering (SERS) bioprobe is reported for the first time with outstanding ultrasensitive specificity, excellent stability of the signal, and good biocompatibility for the detection of CTCs. The TiO2 NPs were encoded with alizarin red (AR) and functionalized with reduced bovine serum protein (rBSA) and folic acid (FA). The limit of detection (LOD) for 4-mercaptobenzoic acid (4-MBA) and AR molecules adsorbed on the TiO2 SERS substrate is 5 × 10−7 M. The designed TiO2-based SERS bioprobe can be effectively utilized in detecting four diverse types of cancer cells in rabbit blood, which shows good sensitivity of the SERS detection technology. Finally, precise targeting of CTCs based on the SERS bioprobe with the function of fluorescence imaging is also confirmed by the fluorescence colouration test. This work offers a novel strategy for CTC detection and the development of non-noble metal semiconductor-based SERS platforms for tumor diagnosis.

研究领域: 生物医学工程 · 癌症诊断
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Visual and quantitative determination of KAT Tip60 activity in circulating tumor cells using a smartphone

Yanmei Lu,Jiayue Liu,Yufang Hu,Wenjun Dong,Caizhao Cheng,Zhihe Qing,Shun Zhang

Visual detection of histone acetylation in cells is highly desirable for medical diagnostics, particularly in cancer. Currently, a single substrate-indicated multi-mode visual platform has been developed for detecting the activity of acetyltransferase (KAT Tip60) in circulating tumor cells (CTCs) of esophageal cancer. o-Phenylenediamine (OPD) serves as a single indicator in our constructed multi-mode analytical method, where the introduction of Cu(II) stimulates a change in fluorescent/UV–vis signals and colors. However, coenzyme A (CoA), a byproduct of the acetylation process, effectively prevents the interaction between Cu(II) and OPD, and this competitive reaction is aptly associated with the KAT Tip60-domonicated acetylation process. Good linear relationships are observed between the optical signals in the multi-mode method and the logarithms of the Tip60 concentration, with detection limits of 0.0045 ng/mL (fluorescence) and 0.058 ng/mL (UV–vis), respectively, calculated as 3σ/slope. To meet the needs of smart/precision medicine, a smartphone-based visualization approach tailored to the red-green-blue (RGB) color space is developed via Cu(II)-OPD redox catalysis. This approach is successfully employed for the analysis of Tip60-indicated acetylation in CTCs of esophageal cancer. This study establishes an important foundation for advancing RGB color-based smartphone modes for actual analyses, and integrating another catalytic unit based on the single OPD substrate presents a viable strategy for analyzing other biomarkers in cancer-targeted clinical applications.

研究领域: 医学诊断 · 癌症研究 · 生物化学
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Alexandria Engineering Journal · 2024 · IF 6.2

Development of a C3N4-based electrochemical sensing platform for the detection of circulating tumor cells in blood

Zhenlu Wang,Yanlong Shi,Zihan Xu,Mengmeng Sun,Xin Shen,Kun Wu,Mingxin Yu,Le Zhang,Guohua Yu

This study presents a cancer diagnostics method through the development of a graphitic carbon nitride (g-C 3 N 4 )-based electrochemical sensor for detecting circulating tumor cells (CTCs) in blood. Utilizing the unique properties of g-C 3 N 4 nanosheets combined with gold nanoparticles functionalized with DNA aptamers, the sensor exhibits remarkable sensitivity and selectivity in CTC detection. The aptamers specifically target cell surface biomarkers, enabling the precise capture and quantification of CTCs. The sensor's detection limit is an impressive 5 cells/mL, with a broad detection range from 10 to 10 5 cells/mL. This high-performance sensing platform not only achieves rapid and accurate quantification of CTCs but also demonstrates robustness against interference from other cell types, making it highly suitable for clinical applications. The optimized conditions for aptamer-functionalized nanoparticle concentration and incubation time ensure the sensor's efficacy, as validated in spiked blood samples. This work provides a practical and efficient approach for non-invasive cancer diagnostics, offering significant improvements over existing methods in terms of simplicity, sensitivity, and specificity for early detection and monitoring of cancer progression.

CAS / MDL: 108-78-1 68-04-2
研究领域: 生物医学工程 · 癌症研究 · 纳米技术
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BIOSENSORS & BIOELECTRONICS · 2025 · IF 10.5

A facile liquid biopsy assay for highly efficient CTCs capture and reagent-less monitoring of immune checkpoint PD-L1 expression on CTCs with non-small cell lung cancer patients

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 · 肿瘤学 · 分子生物学
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ANALYTICAL BIOCHEMISTRY · 2023 · IF 2.9

An integrated electrochemical immunosensor based on Pd–Ir cubic nanozyme and Ketjen black for ultrasensitive detection of circulating tumor cells

Xuhuai Fu,Yunyao Lu,Yang Peng

Ultrasensitive detection of circulating tumor cells (CTCs) holds significant clinical importance in monitoring metastasis and therapeutic outcomes. In this study, we have developed a novel electrochemical sensing model based on nanomaterials for highly sensitive and specific determination of CTCs. A gold electrode co-modified with Ketjin black (KB) and Au nanoparticles (AuNPs) exhibits exceptional conductivity. By conjugating palladium-iridium cubic nanozyme (Pd–Ir CNE) with antibodies, we have created a detection probe capable of catalyzing hydrogen peroxide (H 2 O 2 ), thereby amplifying the output signal and resulting in significantly enhanced current on the electrode for detecting CTCs. The constructed immunosensor has achieved a detection limit of 2 cell mL −1 for model MCF-7 cells. Furthermore, the as-constructed electrochemical immunosensor can accurately detect whole blood-spiked target CTCs, showing great promise for clinical applications in early cancer diagnosis and prognosis.

CAS / MDL: 110802-84-1
研究领域: 医学诊断 · 生物材料学 · 肿瘤学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2023 · IF 3.4

Bifunctional electrochemical biosensor based on PB-MXene films for the real-time analysis and detection of living cancer cells

Xue Su,Qiannan You,Linlin Zhuang,Zhimin Chang,Mingfeng Ge,Li Yang,Wen-Fei Dong

Circulating tumor cells (CTCs) are important prognostic markers for cancer diagnosis and metastasis, and their detection is an important means to detect cancer metastasis. Herein, we construct a novel bifunctional electrochemical biosensor based on the PB-MXene composite films. A simple electrostatic self-assembly approach was employed to prepare a film composed of PB nanocubes on the MXene substrates. Given that the PB is an artificial peroxidase for H 2 O 2 sensing, the PB-MXene films can realize the real-time monitoring of H 2 O 2 secretion from living CTCs. Besides, the anti-CEA attached biosensors can be utilized to quantify the corresponding CTCs. The synergic effects of the MXene with a large specific area and PB with enzyme-free catalysis for H 2 O 2 resulted in PB-MXene films exhibiting high electrocatalytic and low cytotoxicity for both H 2 O 2 sensing and living CTCs capturing. As a result, the biosensor shows a low detection limit of 0.57 μM towards H 2 O 2 with a wide linear range (1 μM to 500 μM), as well as an excellent sensing performance for CTCs (an extremely low detection limit of 9 cells/mL in a wide linear range of 1.3 ×10 1 to 1.3 ×10 6 cells/mL). Moreover, the prepared biosensor showed satisfactory stability and anti-interference ability for potential applications in clinical cancer diagnosis and tumor metastasis.

CAS / MDL: 7789-24-4
研究领域: 生物医学工程 · 癌症诊断
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BIOSENSORS & BIOELECTRONICS · 2022 · IF 12.545

Dually stimulative single-chain polymeric nano lock with dynamic ligands for sensitive detection of circulating tumor cells

Miao Cui,Xiaoyu Chen,Xu Luo,Zhihang Zhou,Zhiji Chen,Zhengdong Zhou,Xiaoyu Zhou,Heng Zou,Tao Xu,Shubin Wang,Mengsu Yang

Circulating tumor cells (CTCs) are important markers for cancer diagnosis and monitoring. However, CTCs detection remains challenging due to their scarcity, where most of the detection methods are compromised by the loss of CTCs in pre-enrichment, and by the lack of universal antibodies for capturing different kinds of cancer cells. Herein, we report a single-chain based nano lock (SCNL) polymer incorporating dually stimulative dynamic ligands that can bind with a broad spectrum of cancer cells and CTCs overexpressing sialic acid (SA) with high sensitivity and selectivity. The high sensitivity is realized by the polymeric single chain structure and the multi-valent functional moieties, which improve the accessibility and binding stability between the target cells and the SCNL. The highly selective targeting of cancer cells is achieved by the dynamic and dually stimulative nano lock structures, which can be unlocked and functionalized upon simultaneous exposure to overexpressed SA and acidic microenvironment . We applied the SCNL to detecting cancer cells and CTCs in clinical samples, where the detection threshold of SCNL reached 4 cells/mL. Besides CTCs enumeration, the SCNL approach could also be extended to metastasis assessment through monitoring the expressing level of surface SA on cancer cells.

研究领域: 生物医学工程 · 癌症诊断 · 分子生物学
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Materials Today Chemistry · 2025 · IF 6.7

Study on the clinical application value of a new type of magnetic nanomicrospheres that can be used for circulating tumor cell sorting in lung cancer

Hao Feng,Huicong Zhang,Weixue Zhang,Guoliang Tan,Chunxia Sun,Wei Xing,Guolei Li

s Purpose The high incidence and mortality rates of lung cancer pose a great challenge for early detection and prognostic assessment. Liquid biopsy biomarkers based on circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), among others, hold promise for non-invasive detection. The aim of this study was to construct a CTC sorting system that can be used to monitor lung cancer progression and compared with ctDNA for downstream analysis. Results The sorting efficiency of the CTC sorting system for lung cancer cells was 95.70 %, and the system demonstrated the ability to monitor CTC changes and tumor progression in animals. The cutoff value of CTC detection in lung cancer was 7.5/5 mL (Area under the curve [AUC]: 0.9976, 95 % CI: 0.9946–1.000), with a sensitivity of 96.70 % and specificity of 98.41 %, effectively indicating progression. Compared with ctDNA, CTC-based analysis detected a broader genomic mutation spectrum with a concordance rate of 19.90 %, but the detection rate of the genomic mutation spectrum could be expanded by the combined test. Conclusion In this study, we successfully developed a novel clinically feasible CTC sorting system capable of monitoring lung cancer progression, which can be applied to early diagnosis, efficacy assessment, and monitoring tumor progression in lung cancer. In addition, CTC showed low concordance with mutations found in ctDNA, and CTC may have specific mutations independent of ctDNA.

CAS / MDL: 57-88-5 75-09-2
研究领域: 肿瘤学 · 分子生物学 · 医学检验
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JOURNAL OF CELL SCIENCE · 2022 ·Vol. 135 ·期 10 · IF 5.235

Fluid shear stress regulates the survival of circulating tumor cells via nuclear expansion

Xu Zichen,Li Keming,Xin Ying,Tang Kai,Yang Mo,Wang Guixue,Tan Youhua

Distant metastasis mainly occurs through hematogenous dissemination, where suspended circulating tumor cells (CTCs) experience a considerable level of fluid shear stress. We recently reported that shear flow induced substantial apoptosis of CTCs, although a small subpopulation could still persist. However, how suspended tumor cells survive in shear flow remains poorly understood. This study finds that fluid shear stress eliminates the majority of suspended CTCs and increases nuclear size, whereas it has no effect on the viability of adherent tumor cells and decreases their nuclear size. Shear flow promotes histone acetylation in suspended tumor cells, the inhibition of which using one drug suppresses shear-induced nuclear expansion, suggesting that shear stress might increase nuclear size through histone acetylation. Suppressing histone acetylation-mediated nuclear expansion enhances shear-induced apoptosis of CTCs. These findings suggest that suspended tumor cells respond to shear stress through histone acetylation-mediated nuclear expansion, which protects CTCs from shear-induced destruction. Our study elucidates a unique mechanism underlying the mechanotransduction of suspended CTCs to shear flow, which might hold therapeutic promise for CTC eradication.

研究领域: 肿瘤学 · 细胞生物学 · 生物力学
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