Nanoscale
·
2017
·Vol. 9
·期 17
·5624-5640
·
IF 7.367
Yu Gao,Xiaodong Xie,Fengqiao Li,Yusheng Lu,Tao Li,Shu Lian,Yingying Zhang,Huijuan Zhang,Hao Mei,Lee Jia
Rare circulating tumor cells (CTCs) cause >50% of primary colorectal cancer survivors to develop deadly metastasis at 3–5 years after surgery; the current chemotherapies can do nothing about these cells. Herein, we synthesized a novel doxorubicin (DOX)-entrapped mesoporous silica nanoparticle (MSN), covalently-conjugated with two aptamers, for simultaneously targeting EpCAM and CD44, the typical surface biomarkers of colorectal CTCs. The nanomissile can specifically capture the metastasis-prone CTCs spiked in healthy human blood in a competitive-binding manner. The binding not only accurately delivers DOX into the cancer cells via the biomarker-mediated endocytosis to inhibit CTC viability through the DOX-dependent mechanism, but also inhibits the adhesion of cancer cells to the endothelium and the consequent transmembrane migration through the DOX-independent mechanism. The molecular entity of the conjugate and its pharmaceutical DOX encapsulation-releasing capacity are well-demonstrated via various physiochemical characterizations including gel electrophoresis, which proves the >8-hour biostability of the nanomissile in blood, long enough for it to chase CTCs in mice and synergistically inhibit the CTC-induced lung metastasis more potently than its single aptamer-conjugated counterparts and DOX itself. The present strategy may pave a new avenue for safe and effective cancer metastasis chemoprevention.
研究领域:
纳米技术
·
癌症研究
·
药学科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
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.
研究领域:
癌症免疫治疗
·
生物医学工程
·
纳米技术
·
光学材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Pei Wang,Bohui Zhou,Ziye Liu,Yining Zhao,Robert Chunhua Zhao,Jinhui Peng,Juan Zhang
The accurate detection of immune checkpoint molecules on the surface of tumor cells is of great significance for immunotherapy. Herein, we propose a method based on cellular interface supported cascade signal amplification mediated by CRISPR/Cas13a system for in situ analysis of immune checkpoint molecules on bladder cancer cells. CD47 and EpCAM on bladder cancer cells can be sensitively monitored through T7 transcription amplification, CRISPR/Cas13a system and HCR triple signal amplification. Moreover, the established method can specifically differentiate EpCAM and CD47 positive bladder cancer cells and well serve for the evaluation of two kinds of membrane protein inhibitors. In a word, the method we proposed can successfully realize in situ analysis of immune checkpoint molecules on bladder cancer cells for guiding immunotherapy.
研究领域:
癌症生物学
·
分子生物学
·
免疫学
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2014
·
IF 5.9
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 44
·22574-22585
·
IF 6.895
Tian Gao,Pi Ding,Wenjing Li,Zhili Wang,Qiao Lin,Renjun Pei
Circulating tumor cells (CTCs) acquire mesenchymal markers (e.g., N-cadherin) and lose epithelial markers (e.g., epithelial cell adhesion molecule, EpCAM) during the epithelial-mesenchymal transition (EMT) and are therefore ideal biomarkers of tumor metastasis. However, it is still a challenge to efficiently capture and detect circulating tumor cells with different phenotypes simultaneously. In this work, to obtain aptamers targeting N-cadherin in the native conformation on live cells, we established stable N-cadherin overexpressing cells (N-cadherin cells) and used these cells to identify a panel of N-cadherin-specific aptamers through the cell-SELEX approach. Two aptamer candidates obtained after 12 rounds of selection showed a low equilibrium dissociation constant in the nanomolar range, indicating high binding affinity. The truncated aptamer candidate NC3S showed the highest binding affinity to N-cadherin cells with a low Kd value of 20.08 nM. The SYL3C aptamer was reported to target cancer cell surface biomarker EpCAM. Then, we synthesized two kinds of aptamer-modified magnetic nanoparticles (SYL3C-MNPs and NC3S-MNPs). Both SYL3C and NC3S aptamers possess excellent capture specificity and efficiency for the target cells. The aptamer–MNP cocktail exhibits a considerable capture efficiency and sensitivity for rare cancer cells of epithelial and mesenchymal phenotypes. Furthermore, no CTCs were found in blood samples from healthy donors, while CTCs were successfully isolated by using the aptamer–MNP cocktail for 15 out of 16 samples collected from patients. In summary, the two kinds of aptamer-modified MNPs could be utilized as a promising tool for capturing CTCs from clinical samples.
研究领域:
生物技术
·
肿瘤学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 9
·1712-1723
·
IF 4.543
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2023
·Vol. 190
·期 8
·1-9
·
IF 5.7
Xia Qing,Zheng Jintao,Bu Jianlan,Li Rui,Li Xinxin,Fan Shuting,Ling Kai,Jiang Hongyan
The development and performance of a DNA probe adsorbing Mn 2+ -modified black phosphorus (BP@Mn 2+ /DNA) hybrid nanosensor is reported that enables rapid detection of cancer-derived exosomal microRNAs (miRNAs) and exosomes. This two-dimensional (2D) nanosensor can spontaneously penetrate the lipid bilayer of exosome membranes owing to its ultra-thin geometry. Subsequently, the adsorbed probe specifically hybridizes with the target miRNA and then dissociates from the nanosensor surface, generating fluorescent signals. Therefore, the BP@Mn 2+ /DNA nanosensor can differentiate between colorectal cancer (CRC) cell-derived exosomes and those derived from intestinal epithelial cells through sensing of exosomal miRNAs. Furthermore, when the epithelial cell adhesion molecule (EpCAM) aptamer is adsorbed onto BP@Mn 2+ instead of the miRNA probe, the nanosensor is able to distinguish exosomes derived from the plasma of CRC patients from those of healthy controls by the recognition ability of the EpCAM aptamer. By utilizing this nanosensor, we were able to effectively differentiate cancer-derived exosomes through the direct detection of miRNA-21 within the exosomes, as well as the identification of specific exosomal membrane proteins. This nanosensor design paves the way for the development of rapid and efficient cancer-derived exosomal miRNA and exosome biosensing nanoplatforms. Graphical abstract
研究领域:
纳米技术
·
癌症生物学
·
分子诊断
·
生物传感器
·
细胞外囊泡
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2018
·Vol. 29
·期 8
·084002
·
IF 3.404
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
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
·
IF 10.257
Juan Cai,Huawei Shen,Yonghong Wang,Yang Peng,Sitian Tang,Yalin Zhu,Qian Liu,Baiying Li,Guoming Xie,Wenli Feng
Accurate detection of circulating tumor cells (CTCs) has a pivotal role in the metastasis monitoring and prognosis of tumor. In this work, an ultrasensitive electrochemical cytosensor was developed based on excellent electrocatalytic materials and a dual recognition strategy. Herein, novel branched PtAuRh trimetallic nanospheres (b-PtAuRh TNS) were synthesized for the first time by a facile one-pot method, which had a huge specific surface area and outstanding catalytic activity. B-PtAuRh TNS linked with aptamers targeting mucin1 (MUC1) were served as signal tags to amplify the signal. As electrode modified material, the nanocomposites of Cabot carbon black (BP2000) and AuNPs were used to improve the electron transfer efficiency of electrode. In addition to using b-PtAuRh TNS labeled anti-MUC1 aptamers as signal probes, anti-EpCAM antibodies were worked as capture probes to achieve dual recognition of target cells. In other words, only cells expressing both MUC1 and EpCAM could produce electrochemical signal. The constructed cytosensor presented a wide linear range (5 - 1 × 10 6 cells mL −1 ) and a low detection limit (1 cell mL −1 ). It was worth noting that the proposed cytosensor could detect CTCs in clinical blood samples. To sum up, the developed cytosensor might become a promising detection platform for cancer diagnosis and tumor metastasis.
研究领域:
生物医学工程
·
纳米技术
·
癌症研究
·
电化学
·
生物传感器
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
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
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2016
·Vol. 12
·期 19
·2595-2608
·
IF 8.315
Yu Gao,Songen Gu,Yingying Zhang,Xiaodong Xie,Ting Yu,Yusheng Lu,Yewei Zhu,Wenge Chen,Huijuan Zhang,Haiyan Dong,Patrick J. Sinko,Lee Jia
The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can prevent cancer metastasis by restraining CTC activity and their adhesion-invasion to vascular intima.
研究领域:
纳米技术
·
癌症生物学
·
药学
·
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）