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Materials Today Bio · 2025 · IF 10.2

Targeting Capture and Eradicate Circulating Tumor Cells by Activated Platelet derived vehicle for inhibiting Triple-Negative Breast Cancer Metastasis

Hongmei Zhang,Jinlan Jiao,Yongxuan Long,Lina Zhou,Yinhua Lv,Wenqian Wei,Yuxiang Sun,Hao Han,Changrong Chen,Yun Zhu,Weijie Zhang

Circulating tumor cells (CTCs) are cardinal intermediaries in the metastatic cascade, particularly in triple-negative breast cancer (TNBC), owing to their high-affinity interactions that bolster survival and dissemination. Addressing this pivotal mechanism, we have developed APEVs@DOX, a pioneering biomimetic delivery system. Utilizing activated platelet membranes as a scaffold, APEVs@DOX recapitulates the natural affinity between platelets and CTCs, enabling targeted delivery of doxorubicin. Our results, substantiated by meticulous in vitro and in vivo experimentation, revealed 78% reduction in lung metastasis nodules in murine models relative to controls, affirming APEVs@DOX's proficiency in CTCs capture and eradication. This study not only illuminates the potential of CTCs-targeted therapies in the precision medicine armamentarium for TNBC but also contributes empirical data to guide the strategic design of anti-metastatic interventions. The therapeutic impact of APEVs@DOX in curtailing metastatic spread offers a beacon of hope for advancing TNBC treatment paradigms.

CAS / MDL: 25316-40-9
研究领域: 肿瘤学 · 药剂学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LAB ON A CHIP · 2019 ·Vol. 19 ·期 15 ·2549-2556 · IF 6.914

Precise and non-invasive circulating tumor cell isolation based on optical force using homologous erythrocyte binding

Xuejia Hu,Daoming Zhu,Ming Chen,Keke Chen,Hailiang Liu,Wei Liu,Yi Yang

Precise isolation of circulating tumor cells (CTCs) is proved to be significant for early cancer diagnosis and downstream analysis. Most of the existing strategies yield low purity or cause unexpected damage to cells because of foreign material introduction. To avoid foreign material caused damage and achieve high efficiency simultaneously, this work presents an innovative strategy using tumor cell targeting molecules to bind homologous red blood cells (RBCs) with tumor cells, which results in obvious optical constant differences (both size and mean refractive index) between CC-RBCs (RBC conjugated CTCs) and other blood cells. Then the modified CTCs can be precisely separated under laser illumination in an optofluidic system. Experiments show that CTCs are efficiently modified with erythrocytes and finally isolated from blood at high purity (more than 92%) and a high recovery rate (over 90%). In the whole process, CTCs are proved to keep membrane and function integrity. The combination of homologous RBC binding and an optofluidic system will provide a convenient tool for cancer early diagnosis and treatment monitoring, which exhibits good performance in CTC non-invasive and precise isolation, thus showing great potential.

研究领域: 医学工程 · 肿瘤学 · 光学
✓ 已验证 DOI PubMed 高影响因子
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Nanoscale · 2023 ·Vol. 15 ·期 8 ·3872-3883 · IF 6.7

A multifunctional black phosphorus nanosheet-based immunomagnetic bio-interface for heterogeneous circulating tumor cell capture and simultaneous self-identification in gastric cancer patients

Yifan Zuo,Yi Xia,Wenwen Lu,Yue Li,Yang Xiao,Shuai Gao,Zhiyi Zhou,Hao Xu,Xingqing Feng,Chenglin Li,Yanyan Yu

A single epithelial cell adhesion molecule (EpCAM) for circulating tumor cell (CTCs) isolation has been proved to be low in efficiency as it fails to recognize EpCAM-negative CTCs. Meanwhile, the current immunocytochemical (ICC) identification strategy for the captured cells is tedious and time-consuming. To address these issues, we designed a dual-labeled fluorescent immunomagnetic nanoprobe (BP–Fe3O4–AuNR/Apt), by loading magnetic Fe3O4 nanoparticles and gold nanorods (AuNRs) onto black phosphorus (BP) nanosheets and then linking them with Cy3-labeled EpCAM and Texas red-labeled tyrosine protein kinase 7 (PTK7) aptamers, which created a high-performance bio-interface for efficient, heterogeneous CTC capture and rapid self-identification with high accuracy. As few as 5 CTCs could be captured from 1.0 mL PBS, mixed cell solution and lysed blood. What's more, the presence of BP and AuNRs on this capturing interface also allowed us to preliminarily investigate the potential photothermal therapeutic effect of the probe toward CTC elimination. The applicability of the probe was further demonstrated in gastric cancer patients. By detecting the number of CTCs in the blood of gastric cancer patients, the correlations between the CTC number and the disease stage, as well as distant metastasis were systematically explored.

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
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NANOTECHNOLOGY · 2019 ·Vol. 30 ·期 28 ·285706 · IF 3.399

Capture and separation of circulating tumor cells using functionalized magnetic nanocomposites with simultaneous in situ chemotherapy

Chunmiao Liu,Baochan Yang,Xue Chen,Zunfu Hu,Zhichao Dai,Dongjiang Yang,Xiuwen Zheng,Xilin She,Qingyun Liu

Circulating tumor cells (CTCs) are a type of rare cell that are firstly shed from solid tumors and then exist in the bloodstream. The effective capture and separation of CTCs has significant meaning in cancer diagnosis and prognosis. In this study, novel Fe3O4–FePt magnetic nanocomposites (Fe3O4–FePt MNCs) were constructed by integrating face centered cubic (fcc) FePt nanoparticles (NPs) onto the surface of the Fe3O4@SiO2 core. After further modification with NH2–PEG–COOH and the tumor-targeting molecule tLyP-1, the acquired Fe3O4–FePt MNCs possesses excellent biocompatibility and stability and could efficiently target and capture tLyP-1 receptor-positive CTCs. Based on the acidic microenvironment within cancer cells, the FePt layer could rapidly release active Fe2+ ions, which could catalyze H2O2 into reactive oxygen species (ROS) and further induce in situ apoptosis in cancer cells while having no distinct cytotoxicity to normal cells. Moreover, the Fe3O4@SiO2 core with its intrinsic magnetism has huge potential for the bioseparation of CTCs. The in vitro ROS fluorescence imaging experiments and cell capture and separation experiments indicated that the Fe3O4–FePt MNCs could specifically capture and separate cancer cells in the CTCs model and further induce in situ apoptosis. Therefore, the Fe3O4–FePt MNCs could serve as a promising multifunctional nanoseparator for efficiently capturing CTCs and simultaneously inducing in situ chemotherapy.

研究领域: 生物医学工程 · 癌症诊断与治疗 · 纳米医学
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Polymer Chemistry · 2015 ·Vol. 6 ·期 19 ·3708-3715 · IF 5.52

Efficient cancer cell capturing SiNWAs prepared via surface-initiated SET-LRP and click chemistry

Lulu Xue,Zhonglin Lyu,Yafei Luan,Xinhong Xiong,Jingjing Pan,Gaojian Chen,Hong Chen

Circulating tumor cells (CTCs) exist in extraordinarily low numbers in the blood of patients with solid tumors, and thus the discovery of a more effective, economical and specific way to capture tumor cells is essential and still remains a tremendous challenge. In this work, the glycopolymer, poly(N-acryloyl glucosamine) (PAGA), and TD05 aptamers were combined on silicon nanowire arrays (SiNWAs) to capture Ramos cells through SET-LRP and click chemistry for the first time. The polymerizations showed controllable living features using 2-hydroxyethyl α-bromoisobutyrate (HEBiB) as a sacrificial initiator. In a serum-containing environment, PAGA-modified surfaces could catch small amounts of Ramos cells. Furthermore, the number of captured specific Ramos cells increased extensively compared with the control after the introduction of the aptamer molecule TD05 onto the PAGA-modified surface. A few non-specific Baf3 cells were captured on the surfaces prepared. The results revealed the synergistic effect generated by combining a glycopolymer and aptamer, which could achieve multivalency-enhanced effective and specific cancer cell capturing, thus suggesting that this can be a promising approach for cancer detection.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
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Theranostics · 2014 · IF 7.827

The Architecture and Biological Function of Dual Antibody-Coated Dendrimers: Enhanced Control of Circulating Tumor cells and Their Hetero-Adhesion to Endothelial Cells for Metastasis Prevention

Jingjing Xie,Rongli Zhao,Songen Gu,Haiyan Dong,Jichuang Wang,Yusheng Lu,Patrick J. Sinko,Ting Yu,Fangwei Xie,Lie Wang,Jingwei Shao,Lee Jia

Dissemination of circulating tumor cells (CTCs) in blood and their hetero-adhesion to vascular endothelial bed of distant metastatic secondary organs are the critical steps to initiate cancer metastasis. The rarity of CTCs made their in vivo capture technically challenging. Current techniques by virtue of nanostructured scaffolds monovalently conjugated with a single antibody and/or drug seem less efficient and specific in capturing CTCs. Here, we report a novel platform developed to re-engineer nanoscale dendrimers for capturing CTCs in blood and interfering their adhesion to vascular endothelial bed to form micrometastatic foci. The nanoscale dendrimers were spatiotemporally accommodated with dual antibodies to target two surface biomarkers of colorectal CTCs. Physiochemical characterization, including spectra, fluorescence, electron microscope, dynamic light scattering, electrophoresis, and chromatography analyses, was conducted to demonstrate the successful conjugation of dual antibodies to dendrimer surface. The dual antibody conjugates were able to specifically recognize and bind CTCs, moderately down-regulate the activity of the captured CTCs by arresting them in S phase. The related adhesion assay displayed that the dual antibody conjugates interfered the hetero-adhesion of CTCs to fibronectin (Fn)-coated substrates and human umbilical vein endothelial cells (HUVECs). The dual antibody conjugates also showed the enhanced specificity and efficiency in vitro and in vivo in restraining CTCs in comparison with their single antibody counterparts. The present study showed a novel means to effectively prevent cancer metastatic initiation by binding, restraining CTCs and inhibiting their hetero-adhesion to blood vessels, not by traditional cytotoxic-killing of cancer cells.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
✓ 已验证 DOI PubMed 高影响因子
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TALANTA · 2024 · IF 5.6

Colorimetric detection of circulating tumor cells in breast cancer based on ladder-branch hybridization chain reaction and DFs/AuNCs nanozyme

Dongxia Ren,Hua Wei,Na Li,Wenda Fu,Zhijun Huang,Longfei Yang,Shijie Mu

Breast cancer is the most common malignant tumor in women, which accounts for 6.9% of all cancer-related deaths. Early diagnosis is crucial for making the best clinical decision and improving the prognosis of patients. Circulating tumor cells (CTCs) have been regarded as significant tumor biomarkers. Herein, we designed a colorimetric biosensor for breast cancer CTCs quantification based on ladder-branch hybridization chain reaction (HCR) and DNA flowers/gold nanoclusters (DFs/AuNCs) nanozyme. With the assistance of complementary DNA labeled on magnetic beads (MBs), the cleavage products of RNA-cleaving DNAzymes (RCDs) could be rapidly captured, subsequently triggering ladder-branch HCR. In addition, the DFs/AuNCs nanozyme was applied for colorimetric analysis, which further improved the sensitivity for the detection of target CTCs. Benefiting from specific RCDs, ladder-branch HCR and DFs/AuNCs, we achieved a superior detection limit of 3 cells/mL as well as a broad linear range of 10 cells/mL to 10 4  cells/mL. Conclusively, this colorimetric biosensor achieved sensitively and selectively detection of breast cancer CTCs without the participation of enzymes at room temperature, which might provide new insight into the early detection of breast cancer.

研究领域: 医学诊断 · 生物传感 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TALANTA · 2025 · IF 6.1

Photoelectrochemical and fluorescent dual-mode sensitive detection of circulating tumor cells based on aptamer DNA-linked CdTe QDs/Bi2MoO6/CdS “double Z-scheme” system

Shihao Duan,Haipeng Zhang,Zhaopeng Liu,Jian Li,Liming Gao,Hong Jiang,Jidong Wang

Herein, a novel dual-mode biosensor integrating photoelectrochemical (PEC) and fluorescence (FL) sensing detection was developed for circulating tumor cells (CTCs) based on aptamer DNA-linked CdTe QDs (Apt-CdTe QDs)/Bi 2 MoO 6 /CdS “dual Z-scheme” sensing system. Apt-CdTe QDs were assembled on FTO/CdS/Bi 2 MoO 6 /cDNA electrode through hybridization with cDNA, resulting in the formation of a double Z-scheme CdS/Bi 2 MoO 6 /CdTe heterostructure that significantly enhanced the separation of photo-generated charge carriers, thereby improving photocatalytic efficiency. Upon the presence of MCF-7 cells, Apt-QDs were captured and subsequently released from the captured electrode, leading to a decrease in photocurrent and an increase in fluorescence intensity, thus enabling effective PEC-FL dual-mode detection. The detection of CTCs exhibited a linear relationship within the concentration range from 50 to 100000 cells mL −1 with limit of detection of 1 cell mL −1 in both PEC and FL modes. This approach effectively corrected systematic errors, improved detection accuracy and sensitivity, and held great potential in the clinical detection of CTCs.

研究领域: 生物传感技术 · 癌症诊断 · 纳米医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMEDICAL MICRODEVICES · 2018 ·Vol. 20 ·期 2 ·1-7 · IF 2.077

An efficient method for CTCs screening with excellent operability by integrating Parsortix™-like cell separation chip and selective size amplification

Jin Xin,Chen Rui,Zhao Shikun,Li Peiyong,Xue Bai,Chen Xiang,Zhu Xinyuan

In this article, an attempt for efficient screening of circulating tumor cells (CTCs) with excellent operability on microfluidic chips was reported. A Parsortix™-like cell separation chip was manufactured in our lab. This chip allowed lateral flow of fluid which increased the flow rate of blood. And, an air valve controlled injection pump was manufactured which allowed eight chips working simultaneously. This greatly facilitated the blood treatment process and saved time. As for the mechanism of screening circulating tumor cells, selective size amplification was utilized. By size amplification of cancer cells, both the hardness and the size of CTCs increased which differentiated them from blood cells. And the modification procedure of beads used for size amplification of cancer cells was optimized. Finally, by integrating the commercialized Parsortix™-like cell separation chip and selective size amplification, a practical method for screening circulating tumor cells was established.

研究领域: 医学工程 · 肿瘤学 · 生物技术
✓ 已验证 DOI PubMed 高影响因子
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Small · 2021 ·Vol. 17 ·期 18 ·2007796 · IF 13.281

Cell-Released Magnetic Vesicles Capturing Metabolic Labeled Rare Circulating Tumor Cells Based on Bioorthogonal Chemistry

Ke Kang,Xiaoxi Zhou,Yujia Zhang,Nanhang Zhu,Guohao Li,Qiangying Yi,Yao Wu

Capture of circulating tumor cells (CTCs) with high efficiency and high purity holds great value for potential clinical applications. Besides the existing problems of contamination from blood cells and plasma proteins, unknown/down-regulated expression of targeting markers (e.g., antigen, receptor, etc.) of CTCs have questioned the reliability and general applicability of current CTCs capture methodologies based on immune/aptamer-affinity. Herein, a cell-engineered strategy is designed to break down such barriers by employing the cell metabolism as the leading force to solve key problems. Generally, through an extracellular vesicle generation way, the cell-released magnetic vesicles inherited parent cellular membrane characteristics are produced, and then functionalized with dibenzoazacyclooctyne to target and isolate the metabolic labeled rare CTCs. This strategy offers good reliability and broader possibilities to capture different types of tumor cells, as proven by the capture efficiency above 84% and 82% for A549 and HepG2 cell lines as well as an extremely low detection limitation of 5 cells. Moreover, it enabled high purity enrichment of CTCs from 1 mL blood samples of tumor-bearing mice, only ≈ 5–757 white blood cells are non-specific caught, ignoring the potential phenotypic fluctuation associated with the cancer progression.

研究领域: 医学 · 生物技术 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

DNA bridged polycrystalline Cu2+-NMOFs for electrochemical detection of mesenchymal circulating tumor cells

Ying Peng,Xiong Zhao,Menglu Li,Yin Yue,Chengying Pan,Taiyuan Li,Sha Ou,Zuquan Hu

The analysis of mesenchymal circulating tumor cells (CTCs) with enhanced migratory is important in the diagnosis and metastasis prediction of cancer. In this work, an efficient electrochemical biosensor has been proposed for the sensitive analysis of mesenchymal CTCs. In our design, the capture antibody modified on the electrode surface can specifically recognize cell-surface vimentin, which is a specific biomarker of mesenchymal CTCs. In the meantime, polycrystalline Cu 2+ -NMOFs with excellent mimic peroxidase property assembled by functional nucleic acids are used as the signal probes . After capturing the mesenchymal CTCs with the capture antibody, the cholesterol-labeled functional nucleic acids modified on the Cu 2+ -NMOFs polycrystalline structures can serve as an anchor to insert into the cell membrane while bringing the polycrystalline Cu 2+ -NMOFs to the surface of the electrode. Consequently, an obvious enhanced signal is generated for sensitive quantitative of mesenchymal CTCs ranging from 2 × 10 1 to 10 4 cell mL −1 with a detection limit of 5 cell mL −1 . Moreover, the biosensor can be applied to quantitative analysis of mesenchymal CTCs in blood samples of clinical bladder cancer patients with high selectivity and anti-interference ability, showing the great prospect for clinical cancer diagnosis.

研究领域: 生物医学工程 · 癌症诊断 · 分析化学
✓ 已验证 DOI 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

LHRH-targeting surface-enhanced Raman scattering tags for the rapid detection of circulating tumor cells

Rui Tang,Ran Hu,Xuehua Jiang,Feng Lu

The rapid and simple detection of circulating tumor cells (CTCs) can enable early diagnosis and improve prognosis in cancer patients. Here, we fabricated luteinizing hormone releasing hormone (LHRH)-conjugated surface-enhanced Raman scattering (SERS) tags to detect CTCs expressing LHRH receptors (LHRHRs) in mouse blood. With optimization, 50 μM 4-mercaptobenzoic acid (pMBA) as reporter molecule and 20 μl of 20 mg/ml reduced bovine serum albumin(rBSA) as protecting layer resulted in the most stable SERS tag suspension. Cultures of HeLa cells, which overexpress LHRHRs, were then used to evaluate the selectivity, sensitivity, and cytotoxicity. Mouse blood was spiked with or without HeLa cells were used to test the practical application of our SERS tag-mediated CTC detection method. In consequence, CTCs can be rapidly detected in the mouse blood in a specific and sensitive manner down to the 5 cells/ml CTC concentration. Additionally, a good linear relationship was observed between CTC concentration and signal intensity. Therefore, this inexpensive method using LHRH-targeting SERS tags rapidly detects CTCs and could prove to be a novel platform for point-of-care testing in cancer patients.

研究领域: 医学 · 生物技术 · 肿瘤学
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