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iScience · 2024 · IF 4.6

Hypoxia stimulates CTC-platelet cluster formation to promote breast cancer metastasis

Weijia Zhou,Chengjun Zhu,Peiliang Shen,Jacqueline F. Wang,Gaoshuang Zhu,Yuanyuan Jia,Yueyao Wu,Siliang Wang,Jia Sun,Fang Yang,Yanni Song,Xin Han,Xiaoxiang Guan

Circulating tumor cell clusters/micro-emboli (CTM) possess greater metastatic capacity and survival advantage compared to individual circulating tumor cell (CTC). However, the formation of CTM subtypes and their role in tumor metastasis remain unclear. In this study, we used a microfluidic Cluster-Chip with easy operation and high efficiency to isolate CTM from peripheral blood, which confirmed their correlation with clinicopathological features and identified the critical role of CTC-platelet clusters in breast cancer metastasis. The correlation between platelets and CTM function was further confirmed in a mouse model and RNA sequencing of CTM identified high-expressed genes related to hypoxia stimulation and platelet activation which possibly suggested the correlation of hypoxia and CTC-platelet cluster formation. In conclusion, we successfully developed the Cluster-Chip platform to realize the clinical capture of CTMs and analyze the biological properties of CTC-platelet clusters, which could benefit the design of potential treatment regimens to prevent CTM-mediated metastasis and tumor malignant progression.

CAS / MDL: 9003-11-6
研究领域: 肿瘤学 · 分子生物学 · 癌症研究
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Materials · 2023 ·Vol. 16 ·期 3 ·1189 · IF 3.4

The Adsorption of CTC onto CFBs: A Study on Fabrication of Magnetic Cellulose/Fe3O4 Beads (CFBs) and Adsorption Kinetics

Jing Wang,Ke Shan,Yanhua Tang,Na Wu,Nan Li

Magnetic cellulose/Fe3O4beads (CFBs) were fabricated by dispersing Fe3O4particles in a microcrystalline cellulose (MCC) matrix. The CFBs were characterized by X-ray diffraction (XRD), vibrating sample magnetometry (VSM), energy dispersive X-ray spectrometry (EDS), Brunauer–Emmett–Teller (BET) analysis and scanning electron microscopy (SEM). The adsorption behaviors of CFBs were studied by chlortetracycline hydrochloride (CTC) adsorption experiments. By means of adsorption kinetics and isotherms, the adsorption mechanisms were explored. The results show that quasi-spherical CFBs with a BET surface area as high as 119.63 m2/g were successfully tailored, with the high saturation magnetization (Ms > 40 emu/g) guaranteeing the magnetic separation of CFBs from wastewater. The process of adsorbing CTC onto CFBs involves monolayer chemical adsorption, and the maximum adsorption capacity for CTC estimated by the Langmuir model is 89.53 mg/g. The CFB product shows better adsorption performance in acidic solution than in basic solution.Keywords:magnetic cellulose/Fe3O4;adsorption;CTC;adsorption kinetics

研究领域: 材料科学 · 环境工程 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE · 2025 · IF 3.5

Unraveling the dynamic metabolite changes during the rolling–cutting of CTC black tea at an industrial scale

Qian Pu,Anlan Qu,Minghui Qi,Yanan Liu,Bin Liu,Xin Fang,Yufei Wang,Yuan Yuan,Guangxian Jiang,Shuang Wu,Mingjin Li,Jingyi Xiao,Youyi Huang

BACKGROUND The rolling–cutting process (RCP) is a crucial process in crush–tear–curl (CTC) black tea, but its quality formation is far from clear. This study aims to elucidate the dynamics of sensory quality and metabolites through quantitative descriptive analysis, headspace solid-phase microextraction/gas chromatography–mass spectrometry, and liquid chromatography–tandem mass spectrometry. RESULTS Sixteen key characteristic aromas with ratio of each relative odor activity value (rOAV) to the maximum rOAV (ROAV) ≥ 0.1, variable importance in projection (VIP) > 1, and P < 0.05 were screened out, and linalool, (2 E )-2-nonenal, and ( E )-2-hexenal were the top three ROAVs. The RCP mainly facilitated the release of grassy aromas through fatty acid oxidation while also promoting the synthesis of fruity aromas through monoterpene biosynthesis and phenylpropanoid/benzoid biosynthesis. Additionally, 72 non-volatiles (VIP > 1.50, P < 0.01) were identified as characteristic metabolites, and flavonoids accounted for the largest proportion. RCP accelerated the glycosylation of kaempferol and quercetin to enhance the bitter and astringent attributes. CONCLUSION These findings will promote the comprehension of CTC black tea quality formation in RCP. © 2025 Society of Chemical Industry.

CAS / MDL: 110-38-3
研究领域: 食品科学 · 代谢组学 · 茶叶加工
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Scientific Reports · 2015 ·Vol. 5 ·期 1 ·1-10 · IF 5.578

Multivalent Conjugation of Antibody to Dendrimers for the Enhanced Capture and Regulation on Colon Cancer Cells

Xie Jingjing,Wang Jichuang,Chen Hongning,Shen Weiyu,Sinko Patrick J.,Dong Haiyan,Zhao Rongli,Lu Yusheng,Zhu Yewei,Jia Lee

Circulation tumor cells (CTCs) in the bloodstream of early-stage cancer patients carry the important information about valuable biomarkers and biological properties of primary tumor. However, detection and capture of CTCs are challenging owing to their low concentrations. Traditional technologies have the limited detection sensitivity and the low capture efficiency. We, herein, report an effective approach to specifically bind and capture colon cancer HT29 cells by using multiple Sialyl Lewis X antibodies (aSlex)-conjugated PAMAM dendrimers. The conjugation was characterized by using atom force microscope, UV and fluorescence measurements. The capturing and regulating HT29 cells by the aSlex-coated dendrimer conjugate were analyzed by microscopy and flow cytometry. The results indicated that the conjugate showed the enhanced capture of HT29 cells in a concentration-dependent manner and the maximum capture efficiency of 77.88% was obtained within 1 h-exposure. G6-5aSlex-FITC conjugate showed capture efficiency better than FITC-G6-COOH-5aSlex conjugate. G6-5aSlex-FITC conjugate could specifically capture HT29 cells even when the target HT29 cells were diluted with the interfering cells (e.g., RBCs) to a low concentration. The capture resulted in a concentration-dependent restraint of the cell activity. In conclusion, the aSlex-coated dendrimer conjugate displayed the great potential in capturing and restraining colorectal CTCs in blood.

研究领域: 肿瘤学 · 纳米医学 · 生物化学
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

Improved SERS-Active Nanoparticles with Various Shapes for CTC Detection without Enrichment Process with Supersensitivity and High Specificity

Xiaoxia Wu,Yuanzhi Xia,Youju Huang,Juan Li,Huimin Ruan,Tianxiang Chen,Liqiang Luo,Zheyu Shen,Aiguo Wu

Circulating tumor cells (CTCs) have received more and more attention in medical biology and clinical practice, especially diagnosis, prognosis, and cancer treatment monitoring. The detection of CTCs within the large number of healthy blood cells is a big challenge due to their rarity, which requires a detection method with supersensitivity and high specificity. In this study, we developed three kinds of new nanoparticles with the function of surface-enhanced Raman scattering (SERS) based on spherical gold nanoparticles (AuNPs), gold nanorods (AuNRs), and gold nanostars (AuNSs) with similar particle size, similar modifications, and different shapes for CTC detection without an enrichment process from the blood. The nanoparticles possess strong SERS signal due to modification of 4-mercaptobenzoic acid (4-MBA) (i.e., Raman reporter molecule), possess excellent specificity due to stabilization of reductive bovine serum albumin (rBSA) to reduce the nonspecific catching or uptake by healthy cells in blood, and possess high sensitivity due to conjugation of folic acid (FA) (i.e., a targeted ligand) to identify CTCs. Under the optimized experimental conditions, the results of detection demonstrate that these nanoparticles could all be utilized for CTC detection without enrichment process from the blood with high specificity, and the AuNS-MBA-rBSA-FA is the best one due to its supersensitivity, whose limit of detection (i.e., 1 cell/mL) is much lower than the currently reported lowest value (5 cells/mL).

研究领域: 医学生物学 · 临床检验
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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

Supramolecular probes with force-induced luminescence for the detection of chlortetracycline (CTC) and application in cellular imaging studies

Yinghong Zhou,Yanting Li,Lixue Yang,Xiaoxia Sun,Yu Hu,Yue Sun

An A-D-A π-conjugated fluorescent probe CBTOP, synthesized via Suzuki coupling and Knoevenagel condensation, serves as a specific tool for chlortetracycline (CTC) analysis. It emits fluorescence over 495–622 nm (blue-to-red). Mechanical grinding triggers its microstructure transformation from columnar to coral-like aggregates, identifiable by fluorescence intensity and color. Under varying water contents, CBTOP self-assembles into nanostructures (sheets, vesicles) via π-π stacking and hydrogen bonding. It specifically recognizes CTC with significant fluorescence quenching and emission blue shift, driven by the ICT mechanism (spectroscopically confirmed). With low cytotoxicity, it enables CTC fluorescent imaging in biological systems, offering a novel specific detection strategy with promising applications.

研究领域: 分析化学 · 生物医学工程 · 分子影像学 · 药物分析 · 纳米生物技术
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Tannic Acid (TA)-Functionalized Magnetic Nanoparticles for EpCAM-Independent Circulating Tumor Cell (CTC) Isolation from Patients with Different Cancers

Pi Ding,Zhili Wang,Zeen Wu,Mingchao Hu,Weipei Zhu,Na Sun,Renjun Pei

The majority of current methods of isolating circulating tumor cells (CTCs) rely on a biomarker. However, the isolation efficiency may be compromised due to the heterogeneity of CTCs. In this work, a simple and broad-spectrum method is established to efficiently isolate the heterogeneous CTCs from patient blood samples using tannic acid (TA)-functionalized magnetic nanoparticles (MNPs). The TA-functionalized MNPs (MNPs-TA) inhibit the nonspecific adhesion of peripheral blood mononuclear cell (PBMC) and enhance cancer cell capture, resulting from the unique interaction between TA and glycocalyx on cancer cells. The MNPs-TA was demonstrated to effectively capture seven kinds of cancer cells (HeLa, PC-3, T24, MAD-MB-231, MCF-7, HT1080, A549) from artificial samples (62.3–93.7%). Moreover, this epithelial cell adhesion molecule (EpCAM)-independent CTC isolation method was also tested using clinical blood samples from patients with different cancers (21 patients), which may provide a universal tool to detect CTCs in the clinic.

研究领域: 纳米技术 · 肿瘤学 · 生物医学工程 · 临床研究
✓ 已验证 DOI PubMed 高影响因子
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CANCER BIOLOGY & THERAPY · 2016 · IF 2.921

Microfluidic chip for isolation of viable circulating tumor cells of hepatocellular carcinoma for their culture and drug sensitivity assay

Yu Zhang,Xiaofeng Zhang,Jinling Zhang,Bin Sun,Lulu Zheng,Jun Li,Sixiu Liu,Guodong Sui,Zhengfeng Yin

Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device. Efficient capture of HCC CTCs originates from the small dimensions of microfluidic channels and enhanced local topographic interactions between the microfluidic channel and extracellular extensions. With the optimized conditions, a capture yield reached > 85% for artificial CTC blood samples. Clinical utility of the system was further validated. CTCs were detected in all the examined 36 patients with HCC, with an average of 14 ± 10/2 mL. On the contrary, no CTCs were detected in healthy, benign liver disease or non-HCC cancer subjects. The current study also successfully demonstrated that the captured CTCs on our CTC-chip were readily released with ethylene diamine tetraacetic acid (EDTA); released CTCs remained alive and could be expanded to form a spheroid-like structure in a 3-dimensional cell culture assay; furthermore, sensitivity of released CTCs to chemotherapeutic agents (sorafenib or oxaliplatin) could be effectively tested utilizing this culture assay. In conclusion, the methodologies presented here offer great promise for accurate enumeration and easy release of captured CTCs, and released CTCs could be cultured for further functional studies.

CAS / MDL: 4420-74-0 9013-20-1
研究领域: 肿瘤学 · 生物医学工程 · 分子生物学
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ACS Biomaterials Science & Engineering · 2018 · IF 4.432

A Supersensitive CTC Analysis System Based on Triangular Silver Nanoprisms and SPION with Function of Capture, Enrichment, Detection, and Release

Huimin Ruan,Xiaoxia Wu,Chengcheng Yang,Zihou Li,Yuanzhi Xia,Ting Xue,Zheyu Shen,Aiguo Wu

Detection of circulating tumor cells (CTCs) may be applied for diagnosis of early tumors like a liquid biopsy. However, the sensitivity remains a challenge because CTCs are extremely rare in peripheral blood. In this study, we developed a supersensitive CTC analysis system based on triangular silver nanoprisms (AgNPR) and superparamagnetic iron oxide nanoparticles (SPION) with function of capture, enrichment, detection, and release. The AgNPR was encoded with MBA (i.e., 4-mercaptobenzoic acid) and modified with rBSA (i.e., reductive bovine serum albumin) and FA (i.e., folic acid) generating organic/inorganic composite nanoparticle MBA-AgNPR-rBSA-FA, which has the function of surface-enhanced Raman scattering (SERS). The optimized SERS nanoparticles (i.e., MBA3-AgNPR-rBSA4-FA2) can be utilized for CTC detection in blood samples with high sensitivity and specificity, and the LOD (i.e., limit of detection) reaches to five cells per milliliter. In addition, the SPION was also modified with rBSA and FA generating magnetic nanoparticle SPION-rBSA-FA. Our supersensitive CTC analysis system is composed of MBA3-AgNPR-rBSA4-FA2 and SPION-rBSA-FA nanoparticles, which were applied for capture (via interaction between FA and FRα), enrichment (via magnet), and detection (via SERS) of cancer cells from blood samples. The results demonstrate that our supersensitive CTC analysis system has a better sensitivity and specificity than the SERS nanoparticles alone, and the LOD is up to 1 cell/mL. The flow cytometry and LSCM (i.e., laser scanning confocal microscope) results indicate the CTCs captured, enriched, and isolated by our supersensitive CTC analysis system can also be further released (via adding excessive free FA) for further cell expansion and phenotype identification.

研究领域: 生物医学工程 · 肿瘤学 · 纳米技术
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Ultradense Erythrocyte Bionic Layer Used to Capture Circulating Tumor Cells and Plasma-Assisted High-Purity Release

Taoye Zhang,Wei Peng,Wanli Jiang,Kefan Gao,Wei Liu

The isolation and detection of rare circulating tumor cells (CTCs) from patient peripheral blood can help early diagnosis of cancer and evaluation of therapeutic outcomes. At present, most of the available strategies for enriching CTCs face serious problems with purity due to the nonspecific interactions between the capture medium and leukocytes. Inspired by the immune evasion ability of homologous red blood cells (RBCs), we modified the tumor-targeting molecule folic acid (FA) on the surface of RBCs by hydrophobic interactions. Under the treatment of polybrene, the charges on the surface of RBCs are neutralized, which reduces the mutual repulsion force. Furthermore, RBCs treated with polyethylene also have excellent deformability, thereby enabling engineered RBCs to form a dense bionic layer on the adhesive glass slide, which can greatly inhibit the nonspecific adhesion of leukocytes. The bionic layer can achieve high-purity enrichment of tumor cells in phosphate-buffered saline (PBS), and we can achieve high-activity release in plasma. The cell count showed over 80% capture efficiency and over 70% release rate, and the purity of CTCs obtained in the artificial blood sample after release was higher than 90%. The RBC bionic surface coating is notably cost-effective and highly applicable for CTC isolation in clinic practice, and thus provides new prospects for designing cell–material interfaces for advanced cell-based biomedical studies in the future.

研究领域: 肿瘤学 · 生物医学工程 · 细胞生物学 · 分子医学
✓ 已验证 DOI PubMed 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2022 · IF 12.545

TiO2-based Surface-Enhanced Raman Scattering bio-probe for efficient circulating tumor cell detection on microfilter

Xiawei Xu,Jie Lin,Yanhong Guo,Xiaoxia Wu,Yanping Xu,Dinghu Zhang,Xiangzhi Zhang,Xie Yujiao,Jing Wang,Chengyang Yao,Junlie Yao,Jie Xing,Yi Cao,Yanying Li,Wenzhi Ren,Tianxiang Chen,Yong Ren,Aiguo Wu

Circulating tumor cell (CTC) detection as a burgeoning detection strategy can identify the tumor lesion in the early stage, and facilitates the understanding of tumorigenesis, tumor progression, metastasis, and drug-resistance. Herein, we present a novel strategy for in situ isolating and directly detecting CTCs from peripheral blood at single-cell resolution using black TiO 2 (B–TiO 2 )-based Surface-Enhanced Raman Scattering (SERS) bio-probe on a microfilter. CTCs were isolated from blood by microfilter based on the size and deformation difference. The SERS bio-probe was composed of crystal-amorphous core-shell B–TiO 2 nanoparticles (NPs), alizarin red (AR) as Raman reporter molecules, and a thin protective layer of NH 2 -PEG2000-COOH (PEG), which provided sufficient binding sites for target molecule of folic acid (FA). Demonstrated by three cell lines of MCF-7 (folate receptor (FR) positive), A549 and Raw264.7 (FR negative), SERS bio-probe of B–TiO 2 -AR-PEG-FA could distinguish FR positive CTCs from peripheral blood cells efficiently by targeting FR on CTC membranes and ruling out false positive interference of white blood cells (WBCs) with reliability and specificity. Benefiting by these advantages, this strategy enhanced the detection efficiency and veracity, which reduced the detection time within 1.5 h and make the LOD of detection reduced to 2 cells/mL. These features also facilitated successful CTC detection in several clinical cancer patient bloods which illustrates that the integration of microfluidic isolation and SERS detection may open new paths for liquid biopsy.

研究领域: 生物医学工程 · 癌症研究 · 纳米技术 · 分析化学
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VIEW · 2022 ·Vol. 4 ·期 1 ·20220054 · IF 0

Reversible capture and release of circulating tumor cells on a three-dimensional conductive interface to improve cell purity for gene mutation analysis

Yi-Ke Wang,Ming Wang,Shi-Bo Cheng,Yi-Jing Chen,Cui-Wen Li,Min Xie,Wei-Hua Huang

Rare circulating tumor cells (CTCs) are always harvested with large numbers of white blood cells (WBCs) by current CTC isolation techniques, which influences the accuracy of CTC-related gene and protein analysis. Therefore, it is very urgent to develop a method for efficient isolation of CTCs with high purity. In this work, we fabricated a reversibly assembled interface by layer-by-layer assembly of biotinylated poly-(L-lysine-graft-ethylene glycol) (PLL-g-PEG-biotin), streptavidin, and CTC-specific antibody on a three-dimensional conductive scaffold, and further embedded it into a customized microchip for CTC capture. The assembled multilayers increased the roughness of the scaffold, which improved the capture efficiency. Importantly, the PLL-g-PEG-biotin covalently coupled with CTCs could be detached from the scaffold by electrostatic repulsion, and the released CTCs could be recaptured on the conductive scaffold via electrostatic attraction while the WBCs were continuously drifted away. This reversible capture and release strategy significantly improved the purity of CTCs, and pure CTCs were obtained from cancer patients’ blood samples for gene mutation assay, which will be of great significance for assisting cancer diagnosis and treatment in a noninvasive way.

CAS / MDL: 9004-32-4
研究领域: 生物医学工程 · 癌症研究 · 分子生物学 · 生物技术
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