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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 · 2015 · IF 12.881

A Self-Cleaning TiO2 Nanosisal-like Coating toward Disposing Nanobiochips of Cancer Detection

Jingxin Meng,Pengchao Zhang,Feilong Zhang,Hongliang Liu,Junbing Fan,Xueli Liu,Gao Yang,Lei Jiang,Shutao Wang

The advanced nanobiochips have been widely employed in diagnosing some high incidence of diseases because of their portable, low-cost, and highly sensitive features. However, the subsequent disposal of these wastes remains unexposed, probably giving rise to serious environmental pollution and health risks similar to traditional biomedical waste. Here, we have presented a TiO2 nanosisal-like coating for disposing nanobiochip waste via the photoresponsive self-cleaning features of the nanobiochip, demonstrated by the nanochips of cancer detection. Moreover, the high specificity and sensitivity of nanochips can be maintained by integrating unique nanostructured coatings (i.e., nanosisal-like coating) with specific recognition molecules (i.e., anti-EpCAM). Therefore, this study will provide a promising strategy for the design and management of practical nanobiodevices, thereby eliminating the old path “pollute first, clean up later”.

CAS / MDL: 30525-89-4
研究领域: 纳米技术 · 生物医学工程 · 环境科学 · 癌症研究
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TALANTA · 2021 · IF 6.057

Specific recognition and photothermal release of circulating tumor cells using near-infrared light-responsive 2D MXene nanosheets@hydrogel membranes

Qiannan You,Jiahui Peng,Zhimin Chang,Mingfeng Ge,Qian Mei,Wen-Fei Dong

2D materials with attractive optical properties are promising for individualized cancer immunotherapy. Isolation, capture, and release of circulating tumor cells (CTCs) are of great significance for promoting the process of early diagnosis of cancers. MXene nanosheets incorporated gelatin hydrogel offers the possibility of achieving near-infrared (NIR) light response to initiate the photothermal effect. Herein, the design and preparation of Ti 3 C 2 T x MXene nanosheets-embedded thermoresponsive gelatin hydrogel membrane with NIR light-responsive for the specific capture and release of CTCs were reported. The membrane was fabricated by casting Ti 3 C 2 T x -embedded gelatin onto a substrate and then modified with epithelial-cell adhesion-molecule antibody (anti-EpCAM) for the specific recognition and separation of CTCs from whole blood. The captured cells can be released without damage with dual-mode containing temperature-responsive release (gelatin deconstructed at 37 °C) and photothermal site-release (Ti 3 C 2 T x induced by NIR light). Furthermore, we were able to achieve an average efficient release rate of 89 % of captured cells with stable cell viability of 87 % via the NIR light irradiation . This work may provide the promising potential for retrieval of single cells in clinical diagnosis.

CAS / MDL: 7789-24-4
研究领域: 癌症免疫治疗 · 生物医学工程 · 纳米技术 · 光学材料
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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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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 9 ·1712-1723 · IF 4.543

Large-area assembly of halloysite nanotubes for enhancing the capture of tumor cells

Rui He,Mingxian Liu,Yan Shen,Zheru Long,Changren Zhou

Here, polystyrene sulfonate sodium (PSS) modified Halloysite nanotubes (HNTs) were self-assembled into a patterned coating on a glass substrate with ordered nanotube arrays in a slit-like confined space. The microstructure of the formed patterned HNTs coating was investigated. The formed strips are more regular and almost parallel to each other with an increase in HNTs concentration. The HNTs coating formed from the 2% PSS-HNTs dispersion has the maximum nanotube alignment degree. The patterned HNTs coating was employed to capture tumor cells. The tumor cells can be captured by the HNTs coating effectively compared with a smooth glass surface due to the enhanced topographic interactions between the HNTs coating and cancer cells. The HNTs coating prepared from the 2% PSS-HNTs dispersion has the highest capture yield which is due to the ordered nanotube arrangement and the appropriate surface roughness. The HNTs coating was further conjugated with anti-EpCAM, which leads to the capture yield of MCF-7 cells reaching 92% within 3 h. The HNTs coating can capture 8 MCF-7 cells from 1 mL artificial blood samples spiked with 10 MCF-7 cells, showing the promising applications of HNTs in clinical circulating tumor cell capture for early diagnosis and monitoring of cancer patients.

研究领域: 纳米技术 · 生物材料 · 癌症研究 · 生物医学工程
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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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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Simple fabrication of rough halloysite nanotubes coatings by thermal spraying for high performance tumor cells capture

Rui He,Mingxian Liu,Yan Shen,Rong Liang,Wei Liu,Changren Zhou

Here, we reported a fast, low-cost, and effective fabrication method of large-area and rough halloysite nanotubes (HNTs) coatings by thermal spraying of HNTs ethanol dispersions. A uniform HNTs coating with high transparence is achieved with tailorable surface roughness and thickness. Compared with normal cells, the tumor cells can be captured effectively with high capture yield by the HNTs coatings (expect HeLa cells), which is attributed to the enhanced topographic interactions between HNTs coating and cancer cells. HNTs coating formed from 2.5% ethanol dispersions shows the highest tumor cells capture yeild (90%), which is related to the appropriate roughness and anti-EpCAM conjugation. The capture yield of HNTs coating towards MCF-7 cells can be further improved to 93% within 2   h under dynamic shear using a peristaltic pump. The capture yield increases with the incubation time, and the flow rate with 1.25   mL/min leads to the maximum capture yield. The HNTs coatings are also effective for capture of tumor cells spiked in artificial blood samples and blood samples from patients with metastatic breast cancer. More than 90% targeted MCF-7 cells and very small amounts of white blood cells are captured by the anti-EpCAM conjugated HNTs coatings from a blood sample. HNTs are further loaded anticancer drug doxorubicin (DOX) and then thermally sprayed into coatings. The MCF-7 cells captured on DOX loaded HNTs coating display significant membrane rupture characteristic and only 3% cell viability after 16   h. The high capture efficiency of tumor cells by HNTs coating fabricated by the thermal spraying method makes them show promising applications in clinical circulating tumor cells capture for early diagnosis and monitoring of cancer patients. The high killing ability of the DOX loaded HNTs coating can also be designed as an implantable therapeutic device for preventing tumor metastasis.

研究领域: 材料科学 · 生物医学工程 · 癌症研究 · 纳米技术
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BIOSENSORS & BIOELECTRONICS · 2016 · IF 7.476

Simultaneous detection of MCF-7 and HepG2 cells in blood by ICP-MS with gold nanoparticles and quantum dots as elemental tags

Xiaoting Li,Beibei Chen,Man He,Han Wang,Guangyang Xiao,Bin Yang,Bin Hu

In this work, we demonstrate a novel method based on inductively coupled plasma mass spectrometry (ICP-MS) detection with gold nanoparticles (Au NPs) and quantum dots (QDs) labeling for the simultaneous counting of two circulating tumor cell lines (MCF-7 and HepG2 cells) in human blood . MCF-7 and HepG2 cells were captured by magnetic beads coupled with anti-EpCAM and then specifically labeled by CdSe QDs-anti-ASGPR and Au NPs-anti-MUC1, respectively, which were used as signal probes for ICP-MS measurement. Under the optimal experimental conditions, the limits of detection of 50 MCF-7, 89 HepG2 cells and the linear ranges of 200-40000 MCF-7, 300-30000 HepG2 cells were obtained, and the relative standard deviations for seven replicate detections of 800 MCF-7 and HepG2 cells were 4.6% and 5.7%, respectively. This method has the advantages of high sensitivity, low sample consumption, wide linear range and can be extended to the simultaneous detection of multiple CTC lines in human peripheral blood.

研究领域: 分析化学 · 癌症研究 · 纳米技术 · 生物医学工程
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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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