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
·
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
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Chenglin Li,Rui Li,Xueyuan Wu,Yifan Zuo,Guixiang Xiong,Meng Huang,Yuqing Sun,Rong Liao,Yang Xiao,Lili Hu,Chao Gao,Yanyan Yu
Circulating tumor cells (CTC) have been represented by different phenotypes due to the epithelial–mesenchymal transition (EMT), which are epithelial CTC (E-CTC), mesenchymal CTC (M-CTC), and mixed (epithelial, mesenchymal) CTC (EM-CTC). Limited work has systematically discussed the associations of CTC number, especially proportions of E-CTC, M-CTC, and EM-CTC in total CTC, with colorectal cancer (CRC) progressions via a simple method with high performances. To achieve this goal, this paper presents the fabrication of a novel anti-nonspecific adsorption immunomagnetic platform called Fe3O4@SiO2@PTMAO@Aptamer, which was obtained by modifying polymeric trimethylamine N-oxide (PTMAO) on magnetic Fe3O4@SiO2, which was then linked with dual aptamers of an epithelial cellular adhesion molecule (EpCAM) and cell surface vimentin (CSV), targeting different CTC phenotypes. Results demonstrated that the abundant coating of PTMAO on Fe3O4@SiO2 improved the anti-nonspecific adsorption and noncell adhesion abilities of the immunomagnetic particles and could capture heterogeneous CTC with higher efficiency within 10 min. These excellent performances of Fe3O4@SiO2@PTMAO@Aptamer allowed us to inspect the correlations of numbers of E-CTC, M-CTC, EM-CTC, or proportions of them in total CTC with clinical information on CRC patients in detail. Our data innovatively and clearly revealed that the captured CTC, especially M-CTC proportion, displayed more close associations with progression, diagnosis, surgery, and chemotherapeutic effects for CRC patients. Overall, we believe that our approach will bring a new understanding of CTC-based liquid biopsy for cancer diagnosis and treatment.
研究领域:
癌症生物学
·
生物医学工程
·
临床肿瘤学
·
分子诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Yonghao Wang,Dengwang Luo,Yao Fang,Wanhao Wu,Yongjing Wang,Yaokun Xia,Fang Wu,Chunyan Li,Jianming Lan,Jinghua Chen
Exosomes may be used as a crucial medium for the early diagnosis and potential therapy of tumors because of containing a variety of biological information. Therefore, the accurate quantitative analysis of exosomes is especially important in the biomedical field. Herein, we proposed a washing-free aptasensor based on luminescence resonance energy transfer (LRET) between rare-earth doped upconversion nanoparticles (UCNPs) donor and tetramethyl rhodamine (TAMRA) acceptor for highly sensitive detection of exosomes. Therein, the combination of UCNPs and TAMRA can be achieved through the coupling of aptamers to the epithelial cell adhesion molecule (EpCAM), the highly expressed surface proteins of the exosomes. Therefore, when the system of UCNPs-TAMRA in the presence of exosomes is excited by near-infrared light at 980 nm, TAMRA emits yellow fluorescence at 585 nm due to LRET. As a result, the fluorescence intensity at 585 nm is linearly correlated to the concentration of exosomes, which is available for the detection and quantification of exosomes. Under optimal conditions, the proposed approach can reach a low limit of detection (LOD) of 80 particles/μL, and effectively reduce the background signal by using UCNPs as an energy donor. Moreover, this proposed aptasensor can be universally applied to the detection of other targets by strictly screening the aptamers.
研究领域:
生物医学工程
·
纳米技术
·
癌症诊断
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2019
·Vol. 411
·期 5
·985-995
·
IF 3.286
Cui Fangchao,Ji Jian,Sun Jiadi,Wang Jun,Wang Haiming,Zhang Yinzhi,Ding Hong,Lu Yong,Xu Dan,Sun Xiulan
We describe a “turn-on” magnetic fluorescent biosensor based on graphene quantum dots (GQDs), Fe 3 O 4 , and molybdenum disulfide (MoS 2 ) nanosheets. It is used for rapid, efficient, and sensitive separation and detection of circulating tumor cells (CTCs). A facile approach (electrochemical synthesis method) for the preparation of photoluminescent GQDs functionalized with an aptamer [epithelial cell adhesion molecule (EpCAM) receptors] and a magnetic agent for one-step bioimaging and enrichment of CTCs is described. MoS 2 nanosheets, as a fluorescence quencher, and the aforementioned aptamer@Fe 3 O 4 @GQD complex were assembled to construct “turn-on” biosensing magnetic fluorescent nanocomposites (MFNs). This system exhibits low cytotoxicity and an average capture efficiency of 90%, which is higher than that of other magnetic nanoparticles on account of the one-step CTC separation method. In addition, the MFNs could quickly identify and label CTCs within 15 min, surpassing other one-step and two-step marker detection methods. Furthermore, because of the presence of aptamers, the MFNs have specific capability to capture CTCs (both low- and high-EpCAM-expressing cells). In addition, high-sensitivity detection of up to ten tumor cells in whole blood was achieved. Therefore, the MFNs have great potential to be used as universal biosensing nanocomposites for fluorescence-guided tumor cell enrichment and bioimaging.
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研究领域:
纳米技术
·
生物传感器
·
癌症研究
·
分子诊断
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2025
·
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
·
肿瘤学
·
生物化学
·
细胞生物学
·
微流控技术
·
基因工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Materials Interfaces
·
2021
·Vol. 8
·期 23
·2101097
·
IF 6.147
Kelin Zhang,Qilin Zhang,Mingxia Yu,Zixiang Wang,Qingyuan Song,Cuiwen Zhu,Xianjia Wu,Rongxiang He,Xingzhong Zhao
A low cost and easily fabricated 3D micro-nano biocompatible calcium phosphate (CaP) microstructure platform is developed to efficiently capture and non-destructively release cancer cells. The thickness of CaP is ≈3 µm after 2.5 min deposition and increased to ≈12 µm after 10 min deposition. The void size between CaP nanosheets is increased when the electro deposition time is increased. This micro-nano bio-interface is suitable for cancer cell capturing and culturing. More than 90% for the EpCAM positive cells are captured on the CaP substrates where the specific anti-EpCAM antibody is modified. On the other hand, the CaP substrates are easily degraded in citric acid (pH 6.0). In this method, 80% of the captured cancer cells can be rapidly released in 2.5 min on the 3 µm thick CaP substrates. The released cancer cells can be well cultured and can keep their viability. This platform is successfully used to capture the CTCs from patients’ peripheral blood with different kinds of cancer. This platform can be applied in the controllable single CTC capture and release analysis, including downstream RT-PCR, gene sequence, and single cell based tumor sphere culture in the future.
研究领域:
生物材料
·
生物医学工程
·
癌症研究
·
纳米技术
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Ying Xu,Yang Xu,Fating Chen,Encheng Li,Chunxiu Hu,Xinyu Liu,Xianzhe Shi,Guowang Xu
Circulating tumor cells (CTCs) are closely related to the early diagnosis, metastasis, and prognosis of cancer. Their efficient capture and precise analysis are significant for advancing precision medicine in cancer treatment. However, CTCs are extremely rare in the bloodstream, and their phenotypes change during the epithelial-mesenchymal transition (EMT), posing significant challenges for effective capture of CTCs. Current methods, which commonly rely on single antibodies or aptamers targeting the epithelial cell adhesion molecule (EpCAM), cannot avoid false negatives due to phenotypic changes. Moreover, traditional “hard interface” nanomaterials are prone to damaging CTCs, affecting subsequent metabolomics analysis. To address these issues, this study proposes dual-aptamer functionalized cell membrane biomimetic magnetic nanoparticles (CCM-IMBs) to efficiently capture CTCs. CCM-IMBs inherit the “homologous targeting” and gentle “soft interface” characteristics of cell membranes and introduce dual aptamers targeting both the epithelial marker EpCAM and the mesenchymal marker CDH2. Experimental results demonstrate that CCM-IMBs exhibit excellent capture efficiency and specificity for target cells, effectively reducing false negatives caused by phenotypic heterogeneity. Furthermore, CCM-IMBs successfully captured CTCs from the peripheral blood samples of four cancer patients with different types of tumors. Additionally, single-cell metabolomics analysis validated that the capture process using CCM-IMBs has minimal impact on the cellular metabolism of CTCs. This research provides a feasible strategy for the efficient capture and in-depth analysis of CTCs.
研究领域:
癌症研究
·
纳米技术
·
生物化学
·
生物医学工程
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2014
·
IF 3.552
Chaoqun Dong,Huiyu Wang,Zhuo Zhang,Tao Zhang,Baorui Liu
Circulating tumor cells (CTC) capture is one of the most effective approaches in diagnosis and treatment of cancers in the field of personalized cancer medicine. In our study, zwitterionic carboxybetaine methacrylate (CBMA) oligomers were grafted onto nylon via atomic transfer random polymerization (ATRP) which would serve as a novel material for the development of convenient CTC capture interventional medical devices. The chemical, physical and biological properties of pristine and modified nylon surfaces were assessed by Fourier transform infrared spectra, atomic force microscope, water contact angle measurements, X-ray photoelectron spectroscopy, protein adsorption, platelet adhesion, and plasma recalcification time (PRT) determinations, etc. The results, including the significant decrease of proteins adsorption and platelets adhesion, as well as prolonged PRTs demonstrated the extraordinary biocompatibility and blood compatibility of the modified surface. Furthermore, we showed that upon immobilization of anti-epithelial cell adhesion molecular (anti-EpCAM) antibody onto the CBMA moiety, the modified nylon surface can selectively capture EpCAM positive tumor cells from blood with high efficiency, indicating the potential of the modified nylon in the manufacture of convenient interventional CTC capture medical devices.
研究领域:
生物医学工程
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
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
·
癌症研究
·
纳米技术
·
材料科学
·
生物技术
✓ 已验证
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2020
·
IF 7.097
Bingchen Zhang,Jiali Jiang,Pengyu Wu,Junjie Zou,Jingqing Le,Juanfang Lin,Chao Li,Bangyue Luo,Yongjie Zhang,Rui Huang,Jingwei Shao
Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel “core‒shell” co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and “green” method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells in vitro, good biosafety of organic tissues and efficient tumor accumulation in vivo . Importantly, UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic effect. The research could provide new ideas for the research and development of self-assembly delivery system in the future, and offer effective intervention strategies for clinical HCC treatment.
研究领域:
纳米技术
·
药理学
·
肿瘤学
·
免疫治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Jianxiang Xu,Yanyan Zhang,Yilu Zheng,Tong Wang,Huan Zhang,Kai Wang,Yu Wang,Gareth R. Williams,Li-Min Zhu
In this work we present a near-infrared (NIR)-operated nanoswitch based on chitosan nanoparticles (EpCAM-CS-co-PNVCL@IR780/IMQ NPs) that induces cascade immunogenic tumor ferroptosis via cytokine storm. The formulation was prepared by loading a photosensitiser (IR780) and an immunotherapeutic drug (imiquimod; IMQ) into temperature- and pH-responsive chitosan-based NPs functionalized with tumor-targeting aptamers. The EpCAM aptamer can chaperone the NPs selectively into cancer cells, and allow them to enter the cell nucleus. In vi tr o and in vi v o assays revelaed that the NPs were able to effectively induce the immunogenic ferroptosis of cancer cells. Under NIR irradiation, EpCAM-CS-co-PNVCL@IR780/IMQ cause cell death in tumors via photothermal therapy. Moreover, IMQ promotes the maturation of dendritic cells (DCs), which then activate cytotoxic T-lymphocytes (CTLs); these T-cells go on to provide immunotherapy of metastatic tumor cells. The metastatic tumor cells can be induced to undergo ferroptosis by the addition of arachidonic acid (AA), which interacts with interferon cytokines (IFN- γ ) released from CTLs.
研究领域:
癌症治疗
·
纳米技术
·
免疫疗法
·
生物医学工程
·
药学科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 19
·12966-12972
·
IF 3.9
Min Dong,Zhihong Gao,Yating Zhang,Jiahui Cai,Jian Li,Panpan Xu,Hong Jiang,Jianmin Gu,Jidong Wang
There has been great interest in the enzymatic cascade amplification strategy for the electrochemical detection of circulating tumor cells (CTCs). In this work, we designed a highly efficient enzymatic cascade reaction based on a multiwalled carbon nanotubes–chitosan (MWCNTs–CS) composite for detection of CTCs. A high electrochemical effective surface area was obtained for a MWCNTs–CS-modified glassy carbon electrode (GCE) for loading glucose oxidase (GOD), as well as a high loading rate and high electrical activity of the enzyme. As a ‘power source’, the MWCNTs–CS composites provided a strong driving power for horseradish peroxidase (HRP) on the surface of polystyrene (PS) microspheres, which acted as probes for capturing CTCs and allowed the reaction to proceed with further facilitation of electron transfer. Aptamer, CTCs, and PS microspheres with HRP and anti-epithelial cell adhesion molecule (anti-EpCAM) antibody were assembled on the MWCNTs–CS/GCE to allow for the modulation of enzyme distance at the micrometer level, and thus ultra-long-range signal transmission was made possible. An ultrasensitive response to CTCs was obtained via this proposed sensing strategy, with a linear range from 10 cell mL−1 to 6 × 106 cell mL−1 and a detection limit of 3 cell mL−1. Moreover, this electrochemical sensor possessed the capability to detect CTCs in serum samples with satisfactory accuracy, which indicated great potential for early diagnosis and clinical analysis of cancer.
研究领域:
生物传感器
·
癌症诊断
·
电化学
·
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）