ACS Sensors
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2023
·
IF 8.9
Jie Wang,Robert Dallmann,Renquan Lu,Jing Yan,Jérôme Charmet
Immunoaffinity-based liquid biopsies of circulating tumor cells (CTCs) hold great promise for cancer management but typically suffer from low throughput, relative complexity, and postprocessing limitations. Here, we address these issues simultaneously by decoupling and independently optimizing the nano-, micro-, and macro-scales of an enrichment device that is simple to fabricate and operate. Unlike other affinity-based devices, our scalable mesh approach enables optimum capture conditions at any flow rate, as demonstrated with constant capture efficiencies, above 75% between 50 and 200 μL min–1. The device achieved 96% sensitivity and 100% specificity when used to detect CTCs in the blood of 79 cancer patients and 20 healthy controls. We demonstrate its postprocessing capacity with the identification of potential responders to immune checkpoint inhibition (ICI) therapy and the detection of HER2 positive breast cancer. The results compare well with other assays, including clinical standards. This suggests that our approach, which overcomes major limitations associated with affinity-based liquid biopsies, could help improve cancer management.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
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临床诊断
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产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2023
·
IF 7
Wenbo He,Zhaoyang Yao,Youlu Diao,Miao Wang,Guoqing Pan
Reversible binding of cell targeting motifs on biomaterial surfaces can be used to mimic the dynamic bioactivities of the extracellular matrix (ECM), thus showing potential to modulate cell behaviours in physiopathologic processes. As the markers of tumour metastasis, circulating tumour cells (CTCs) are especially essential for the diagnosis of cancer. Dynamic display of cancer targeting motifs on biometric interfaces thus enables specific isolation of rare cancer cells and delivery of critical information for cancer therapy. In this work, we report a dynamic biointerface for the reversible binding of cancer-targeting motifs on quartz through molecular recognition between the natural glycopeptide vancomycin (Van) and the D-alanine-D-alanine (AA) dipeptide. This active surface could not only realize specific cancer cell adhesion but also induce nondestructive cell detachment by the competitive addition of the free AA dipeptide. The cell isolation efficiency in the medium could reach 70% within 120 min, showing high specificity and separation efficiency. Furthermore, the dynamic display of cancer-targeting motifs on magnetic beads enabled magnetic cancer cell capture and AA dipeptide-triggered cell release. Therefore, the natural dynamic strategy using noninvasive glycopeptide recognition holds promise for rare cell detection, isolation and cell-based disease diagnosis.
研究领域:
生物材料
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癌症研究
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细胞生物学
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分子识别
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产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
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2022
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IF 12.545
Ying Peng,Bing Lu,Ying Deng,Nana Yang,Genxi Li
Accurate and sensitive assay of specific circulating tumor cells (CTCs) is of importance for the diagnosis, treatment, and metastasis monitoring of cancer. Herein, we have proposed a dual-recognition-controlled electrochemical biosensor in this work for the detection of specific CTCs. To this sensor, two aptamer hairpin probes are designed to be able to separately bind to two adjacent proteins on the cell membrane to activate the associative toehold for strand displacement reaction, which will then trigger a dimer-like rolling cycle amplification reaction, and finally produce significantly amplified electrochemical signals for sensitive quantification of target CTCs. In our design, only the case that the two proteins are simultaneously expressed on the cell membrane can result in obvious signal responses, which may greatly improve the accuracy of CTCs analysis. The proposed biosensor can possess excellent selectivity to distinguish target cells from different cancer cells. Moreover, the combination of rolling cycle amplification and DNA nanostructure capture probes can effectively lower the detection limit to 3 cells mL −1 . Notably, our biosensor can be applied to the assay of the target CTCs in the complex whole blood matrixes, verifying its strong stability and anti-interference. Thus, the as-proposed dual-recognition-controlled electrochemical biosensor may exhibit great promise in clinical cancer diagnosis and personalized medicine.
研究领域:
癌症研究
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生物工程
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电化学
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分子生物学
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临床诊断
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Su Gao,Shuangshuang Chen,Yangyang Liu,Hailei Mao,Qinghua Lu
Single-cell capture and in situ analysis of circulating tumor cells (CTCs) in blood are of great significance for early cancer diagnosis, prognosis, and individualized treatment. However, designing an all-in-one platform that enables not only efficiently specific isolation of CTCs but also in situ analysis of heterogeneity and drug screening is challenging. Here, a cell-imprinted alginate hydrogel (CIAH) interface with all-in-one functions was developed for the capture, in situ analysis, and drug-response study at a single-cell level. Based on the equivalent morphology and “specific odor” left by template cells and supplemented by natural antibody, the CIAH interface exhibited outstanding performance in isolating CTCs from samples suffering from cancers. Beyond capture, the CIAH interface was also able to serve as a high-throughput platform for subpopulation analysis and drug response of heterogeneous CTCs. We demonstrated that the highly integrated multifunctional CIAH interface is a promising new tool for single-cell profiling of phenotypic heterogeneity and guiding of personalized anticancer therapy.
研究领域:
生物医学工程
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肿瘤学
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分子生物学
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药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
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IF 12.1
Jinglin Chen,Zhun Lin,Xin Wan,Jingguo Wang,Yuanqing Zhang
Circulating tumor cell (CTC) detection is crucial for early cancer diagnosis and real-time metastasis monitoring. Conventional immunomagnetic nanomaterials (IMNs) used for CTC enrichment face limitations such as low purity and inefficiency. Although cell membrane-coated IMNs have been explored to reduce nonspecific leukocyte binding, challenges persist, including high membrane consumption, low encapsulation efficiency, and unpredictable membrane orientation. Here, polyethyleneimine-coated magnetic nanoparticles (PEI-MNPs) loaded with a plasmid encoding an anti-EpCAM single-chain variable fragment (scFv) is developed. To enhance intracellular delivery, a microfluidic chip with a fluidic channel oriented perpendicular to the main narrow channel, inducing transient cellular deformation and improving nanoparticle uptake is designed. Once internalized, the PEI-MNPs facilitate intracellular expression of anti-EpCAM scFv, enabling precise recognition and magnetic separation of CTCs. This streamlined microfluidic approach achieves high-throughput, efficient magnetic loading, and genetic engineering of target cells. This method significantly improves CTC enrichment, yielding a purity of 91.9%, compared to 61.2% with commercially available IMNs. By utilizing intact cells as biomimetic carriers for IMN encapsulation, this strategy effectively mimics receptor-ligand interactions in vivo and minimizes nonspecific leukocyte adsorption. This work presents a novel and efficient approach for high-purity CTC isolation, offering promising potential for early cancer diagnosis and metastasis monitoring.
研究领域:
生物医学工程
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纳米技术
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肿瘤学
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生物化学
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细胞生物学
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微流控技术
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基因工程
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
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IF 8.4
Qian Chen,Wenyan Guo,Dan Fang,Ting Li,Lin Chen,Chun Mao,Mimi Wan,Jian Shen
The efficient capture and detection of circulating tumor cells (CTCs) in blood is very important for the early detection of cancer. In this work, efficient detection of CTCs through electrochemical means utilizing Mg-Based micromotors was realized, the prepared Fe 3 O 4 /P/anti-E nanoparticle was subjected to modification using an aldehyde-amine condensation reaction to attach it to the Mg ball. Utilizing the asymmetrical structure of micromotor, we find that the movement range of the magnesium microsphere has obviously improved. On this basis, efficient capture of CTCs can be realized upon the modification of Fe 3 O 4 /P/anti-E with capturing cyclability ability. Such a behavior can be attributed to the anti-E modified on the micromotor can target the epithelial cell adhesion factors on CTCs. Furthermore, A funnel-shaped electrochemical detection device was developed to realize the electrochemical detection of captured CTCs based on the insularity of CTCs. The strategy can potentially provide new visions for the early detection and timely treatment of cancer.
研究领域:
癌症研究
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生物医学工程
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纳米技术
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电化学
✓ 已验证
产品关联
DOI
高影响因子
Chemical Science
·
2020
·Vol. 11
·期 7
·1948-1956
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IF 9.346
Qianying Zhang,Wenjing Wang,Shan Huang,Sha Yu,Tingting Tan,Jian-Rong Zhang,Jun-Jie Zhu
The effective capture, release and reanalysis of circulating tumor cells (CTCs) are of great significance to acquire tumor information and promote the progress of tumor therapy. Particularly, the selective release of multiple types of CTCs is critical to further study; however, it is still a great challenge. To meet this challenge, we designed a smart DNAzyme probe-based platform. By combining multiple targeting aptamers and multiple metal ion responsive DNAzymes, efficient capture and selective release of multiple types CTCs were realized. Sgc8c aptamer integrated Cu2+-dependent DNAzyme and TD05 aptamer integrated Mg2+-dependent DNAzyme can capture CCRF-CEM cells and Ramos cells respectively on the substrate. With the addition of Cu2+ or Mg2+, CCRF-CEM cells or Ramos cells will be released from the substrate with specific selectivity. Furthermore, our platform has been successfully demonstrated in the whole blood sample. Therefore, our capture/release platform will benefit research on the molecular analysis of CTCs after release and has great potential for cancer diagnosis and individualized treatment.
研究领域:
生物技术
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癌症研究
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Le Wang,Song Huang,Qin-Ying Li,Li-Yun Ma,Cong Zhang,Feng Liu,Ming Jiang,Xu Yu,Li Xu
The efficient capture and release of the circulating tumor cells (CTCs) are promising for the CTC related cancer diagnosis and subsequent analysis. However, it is a great challenge to isolate and enrich the rare CTCs from the complex peripheral blood sample, which inhibits its broad translating to the clinical applications. Although various papers reported that the nanostructure substrates can improve the capture efficiency of CTCs, few of researches constructed 3D hierarchical micro/nano-structured microdevice to enhance the efficiency of CTC capture and release with a simple manner. Herein, a bio-inspirited 3D epithelial cell adhesion molecule (EpCAM) aptamer modified rose petal derived ZnO microchip (EpCAM-RPD-ZnO-Chip) was designed to realize efficient capture and release of the CTCs. The 3D rough spherical concave surfaces on the EpCAM-RPD-ZnO-Chip guaranteed the maximum contact with the CTCs, thus improving the capture efficiency. Moreover, simple release of CTCs by dissolving ZnO under moderate acidic condition was achieved. The topographical and target molecular recognition cooperatively contributed to highly efficient capture of CTCs. The scanning electron microscope (SEM) image clearly showed that the filopodias and lamellipodias of CTCs stretched and attached to the ZnO nanomaterials. In sum, the proposed 3D EpCAM-RPD-ZnO-Chip is expected to be a promising tool for capture and release of CTCs in clinical trials, which might lay a foundation for downstream analysis and precise drug susceptibility test for the cancer treatment.
研究领域:
生物医学工程
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癌症研究
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纳米技术
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材料科学
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生物技术
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
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2022
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IF 8.008
Bing Lu,Ying Deng,Ying Peng,Yue Huang,Jiehua Ma,Genxi Li
Capture and analysis of circulating tumor cells (CTCs) from complex matrixes is pivotal for the prediction of cancer metastasis and personalized treatment of cancer. Herein, we propose a strategy for CTC capture by design and fabrication of a polyvalent aptamer network on an electrode surface, which can be further used for the sensitive analysis of CTCs. In our design, the polyvalent aptamer network, which is constructed via a rolling circle amplification reaction, can significantly enhance the cell-binding abilities. Meanwhile, tetrahedral DNA structures previously assembled on the electrode surface will promote the spatial orientation and reduce the steric hindrance effect of the cell capture, thus improving the cell capture efficiency. Importantly, a detectable electrochemical signal can be obtained without additional signal probes by means of target-induced allostery of the DNA hairpin structures. Further studies reveal that the electrochemical response is proportional to the logarithm of the CTC abundance ranging from 102 to 5 × 104 cell mL–1 with a low limit of detection of 23 cell mL–1. Moreover, the proposed capture strategy exhibits excellent stability and anti-interference in human whole blood, indicating its promising potential in clinical diagnosis.
研究领域:
癌症研究
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生物化学
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分子生物学
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电化学
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Ning Xia,Daohong Wu,Haiqing Yu,Wanwan Sun,Xinyao Yi,Lin Liu
Simple, sensitive and rapid detection of circulating tumor cells (CTCs) is of great importance for early diagnosis and therapy of cancers. Overexpression of sugar units on cell surface is related to the phenotypes of many cancers. Based on the boronate ester interaction, we reported the electrochemical and colorimetric detection of CTCs with high simplicity and sensitivity. Specifically, ferroceneboronic acid (FcBA) can be measured by differential pulse voltammetry and 4-mercaptophenylboronic acid (MPBA) can induce the aggregation and color change of gold nanoparticles (AuNPs). CTCs captured by the aptamer-modified magnetic beads (Apt-MBs) can sequestrate FcBA or MPBA molecules by the formation of boronate ester bonds, thus leading to the decrease in the electrochemical signal of FcBA or preventing the MPBA-triggered aggregation of AuNPs. Due to the overexpression of sugar groups on the surface of CTCs, the amplification-free methods exhibited high sensitivity and obviated the use of additional antibody or aptamer for the recognition of captured cells. With MCF-7 cancer cell as the model, 50 cells can be readily determined by the electrochemical and colorimetric methods. The proposed strategy is valuable for probing of cell glycosylation and designing of novel sensing devices for detection of sugar-containing biological macromolecules and cells.
研究领域:
生物化学
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分析化学
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癌症研究
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Ran Huang,Daopeng Fan,Hanghang Cheng,Jian Huo,Shuqi Wang,Hua He,Gaiping Zhang
Background Advanced breast cancer is a highly metastatic tumor with high mortality. Simultaneous elimination of primary tumor and inhibition of neutrophil-circulation tumor cells (CTCs) cluster formation are urgent issues for cancer therapy. Unfortunately, the drug delivery efficiency to tumors and anti-metastasis efficacy of nanomedicine are far from satisfactory.Methods To address these problems, we designed a multi-site attack, neutrophil membrane-camouflaged nanoplatform encapsulating hypoxia-responsive dimeric prodrug hQ-MMAE2 (hQNM-PLGA) for enhanced cancer and anti-metastasis therapy.Results Encouraged by the natural tendency of neutrophils to inflammatory tumor sites, hQNM-PLGA nanoparticles (NPs) could target delivery of drug to tumor, and the acute hypoxic environment of advanced 4T1 breast tumor promoted hQ-MMAE2 degradation to release MMAE, thus eliminating the primary tumor cells to achieve remarkable anticancer efficacy. Alternatively, NM-PLGA NPs inherited the similar adhesion proteins of neutrophils so that NPs could compete with neutrophils to interrupt the formation of neutrophil-CTC clusters, leading to a reduction in extravasation of CTCs and inhibition of tumor metastasis. The in vivo results further revealed that hQNM-PLGA NPs possessed a perfect safety and ability to inhibit tumor growth and spontaneous lung metastasis.Conclusion This study demonstrates the multi-site attack strategy provides a prospective avenue with the potential to improve anticancer and anti-metastasis therapeutic efficacy.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 6
·2383-2393
·
IF 5.251
Wanyun Song,Xinyi Li,Yuquan Zhao,Chaoying Liu,Junying Xu,Huiyu Wang,Tao Zhang
The capture of circulating tumor cells (CTCs) plays a crucial role in the early diagnosis, personalized treatment and postoperative evaluation of malignant tumors. In this study, UV-curable coating technology was combined with antibody immobilization to enable CTC captures on poly(methyl methacrylate) (PMMA) substrates. Controlled amounts of carboxyl groups and polyethylene glycol (PEG) segments were introduced into the coating formulation to facilitate immobilization of antibodies and block non-specific protein adsorption, respectively. Then, anti-EpCAM antibodies were immobilized on functionalized, coated PMMA substrates by EDC/NHS chemistry. Multiple physical, chemical and biological properties were investigated, including hydrophilicity, protein adsorption, platelet adhesion and anticoagulant properties. Thereafter, optimized coatings were applied on the inner wall of PMMA tubes, followed by immobilization of anti-EpCAM antibodies. After perfusion of the tubes with whole blood, enriched with SGC7901 gastric cancer cells that overexpress EpCAM antigens, rapid and efficient capture of the tumor cells was observed. These results provide a basis for further development of devices for the selective capture and enrichment of CTCs, using small blood volumes.
研究领域:
生物医学工程
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癌症研究
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材料科学
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生物材料
✓ 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）