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Materials · 2023 ·Vol. 16 ·期 8 ·3065 · IF 3.4

Three-Dimensional PLGA Nanofiber-Based Microchip for High-Efficiency Cancer Cell Capture

Mengting Qi,Meilin Ruan,Jinjin Liang,Zhengtao Zhang,Chaohui Chen,Yiping Cao,Rongxiang He

A 3D network capture substrate based on poly(lactic-co-glycolic acid) (PLGA) nanofibers was studied and successfully used for high-efficiency cancer cell capture. The arc-shaped glass micropillars were prepared by chemical wet etching and soft lithography. PLGA nanofibers were coupled with micropillars by electrospinning. Given the size effect of the microcolumn and PLGA nanofibers, a three-dimensional of micro-nanometer spatial network was prepared to form a network cell trapping substrate. After the modification of a specific anti-EpCAM antibody, MCF-7 cancer cells were captured successfully with a capture efficiency of 91%. Compared with the substrate composed of 2D nanofibers or nanoparticles, the developed 3D structure based on microcolumns and nanofibers had a greater contact probability between cells and the capture substrate, leading to a high capture efficiency. Cell capture based on this method can provide technical support for rare cells in peripheral blood detection, such as circulating tumor cells and circulating fetal nucleated red cells.Keywords:cancer cells;nanofibers;micropillar;mesoscopic interface;microchip

研究领域: 生物医学工程 · 癌症研究 · 纳米技术 · 微流控
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ACS Nano · 2022 · IF 18.027

Flexible Electronic Catheter Based on Nanofibers for the In Vivo Elimination of Circulating Tumor Cells

Dou Wang,Ruihua Dong,Xuedong Wang,Xingyu Jiang

Clearing circulating tumor cells (CTCs) that are closely related to cancer metastasis and recurrence in peripheral blood helps to reduce the probability of cancer recurrence and metastasis. However, conventional therapies aiming at killing CTCs always cause damage to normal blood cells, tissues, and organs. Here, we report a flexible electronic catheter that can capture and kill CTCs via irreversible electroporation (IRE) with high efficiency. The flexible electronic catheter is assembled from nanofibers (NFs) with liquid metal–polymer conductor (MPC) electrodes. The NFs were modified with an epithelial cellular adhesion molecule (EpCAM) antibody on the surface to improve specific biorecognition and cell adhesion. Whole-body blood can be screened by the catheter repeatedly, during which the EpCAM antibody on a nanofiber can enrich CTCs to the surface of the catheter. Taking advantage of the high specific surface area, the capture efficiency of NF-based catheters for CTCs is 25 times higher than previously reported cases. Furthermore, the number of nonspecifically captured WBCs is less than 10 per mm2 areas of the catheter, compared to their original large number of 4–11 × 106 mL–1 of whole blood, showing good specificity of the flexible electronic catheter. The flexible and biocompatible MPC electrodes have a high killing efficiency of 100% for the captured CTCs in a rabbit model. No noticeable hematologic index and morphological changes of the vessels and major organs were observed, indicating that this electronic catheter had good biocompatibility. The present functional electronic catheter offers an alternative strategy for improving the efficiency of clinical cancer therapy

研究领域: 生物医学工程 · 肿瘤学 · 纳米技术 · 材料科学
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ACS Applied Materials & Interfaces · 2014 · IF 5.9

Carboxybetaine Methacrylate-Modified Nylon Surface for Circulating Tumor Cell Capture

Huiyu Wang,Guofeng Yue,Chaoqun Dong,Fenglei Wu,Jia Wei,Yang Yang,Zhengyun Zou,Lifeng Wang,Xiaoping Qian,Tao Zhang,Baorui Liu

Conventional in vitro circulating tumor cell (CTC) detection methods are always limited by blood sample volume because of the requirement of a large amount of blood. The aim of this study was to overcome the limitation by designing and making an in vivo CTC capture device. In this study, we designed and prepared a kind of proper material to serve the purpose of intervention. A method employing 3-aminopropyltriethoxysilane (γ-APS) as the coupling reagent to graft carboxybetaine methacrylate (CBMA) and to immobilize an anti-epithelial cell adhesion molecular (EpCAM) antibody on Nylon was developed. The results of X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy proved the successful graft of γ-APS and CBMA to Nylon. Furthermore, the predicted improvement in the biocompatibilities of our modified Nylon was confirmed by water contact angle measurement, bovine serum albumin adhesion, platelet adhesion, plasma recalcification time determination, and cytotoxicity tests. The tumor cells adhesion experiment revealed that Nylon with the antibody immobilized on it had an affinity for EpCAM positive tumor cells higher than that of pristine Nylon. Additionally, the capture ability of the CTCs was demonstrated in a nude mouse tumor model using the interventional device made of the modified Nylon wire. The positive results suggest that CBMA-grafted and anti-EpCAM antibody-immobilized Nylon is a promising new material for in vivo CTC capture devices.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
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NANOTECHNOLOGY · 2018 ·Vol. 29 ·期 8 ·084002 · IF 3.404

Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy

Dao-Ming Zhu,Wei Xie,Yu-Sha Xiao,Meng Suo,Ming-Hui Zan,Qing-Quan Liao,Xue-Jia Hu,Li-Ben Chen,Bei Chen,Wen-Tao Wu,Li-Wei Ji,Hui-Ming Huang,Shi-Shang Guo,Xing-Zhong Zhao,Quan-Yan Liu,Wei Liu

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam–RPAuNs. We characterized the capability of the EpCam–RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam–RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam–RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam–RPAuNs can be potentially applied for cancer diagnoses and therapies.

研究领域: 纳米技术 · 癌症研究 · 生物医学工程 · 材料科学 · 诊疗学
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ANALYTICAL CHEMISTRY · 2018 · IF 6.042

Design of a Biocompatible and Ratiometric Fluorescent probe for the Capture, Detection, Release, and Reculture of Rare Number CTCs

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.

CAS / MDL: 16961-25-4 57-13-6
研究领域: 生物医学工程 · 纳米技术 · 癌症生物学 · 分子诊断
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Biomaterials Science · 2019 ·Vol. 7 ·期 6 ·2383-2393 · IF 5.251

Functional, UV-curable coating for the capture of circulating tumor cells

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.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物医学工程 · 癌症研究 · 材料科学 · 生物材料
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RSC Advances · 2023 ·Vol. 13 ·期 19 ·12966-12972 · IF 3.9

Ultrasensitive electrochemical biosensor for detection of circulating tumor cells based on a highly efficient enzymatic cascade reaction

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
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