EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2015
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IF 3.35
Xiaodong Xie,Fengqiao Li,Huijuan Zhang,Yusheng Lu,Shu Lian,Hang Lin,Yu Gao,Lee Jia
Targeted delivery of anticancer agents by functional nanoparticles is an attractive strategy to increase their therapeutic efficacy while reducing toxicity. In this work, doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) were modified with aptamer (Ap) against the epithelial cell adhesion molecule (EpCAM) for targeted delivery of DOX to colon cancer cells. These nanoparticles (Ap-MSN-DOX) were characterized by particle size, zeta potential , aptamer conjugation efficiency, drug encapsulation efficiency, and drug release properties. The in vitro cell recognition, cellular uptake, EpCAM protein inhibition efficiency, and cytotoxicity of Ap-MSN-DOX were also studied. Results demonstrated that EpCAM conjugation increased binding of Ap-MSN-DOX to EpCAM over-expressing SW620 colon cancer cells but not EpCAM-negative Ramos cells, resulting in enhanced cellular uptake and increased cytotoxicity of the DOX in SW620 cells when compared to non-Ap-modified nanoparticles (MSN-DOX). Additionally, Ap-MSN-DOX exhibited significant inhibition effects on the expression of EpCAM on SW620 cells. These results suggested that Ap-MSN-DOX has the potential for the targeted delivery of therapeutic agents into EpCAM positive colon cancer cells to improve therapeutic index while reducing side effects.
研究领域:
药剂学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
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IF 7.5
Zhao Liu,Chen Zhang,Beiming Cui,Yijie Wang,Kaisheng Lim,Kai Li,Jean Paul Thiery,Jun Chen,Chun Loong Ho
Protein-based cancer therapies are considered an alternative to conventional anticancer regimens, providing multifunctional properties while showing low toxicity. However, its widespread use is limited by absorption and instability issues, resulting in higher dosage requirements and a prolonged onset of bioactivity to elicit the desired response. Here, we developed a non-invasive antitumor treatment using designed ankyrin repeat protein (DARPin)-anticancer protein-conjugate that specifically targets the cancer biomarker, epithelial cell adhesion molecule (EpCAM). The DARPin-anticancer proteins bind to EpCAM-positive cancer cells and improve the in vitro anticancer efficacy by over 100-folds within 24 h, where the DARPin-tagged human lactoferrin fragment (drtHLF4) IC50 value is within the nanomolar range. Orally administered drtHLF4 was readily absorbed into the systemic flow of the HT-29 cancer murine model, exerting its anticancer effect on other tumors in the host body. Orally administered drtHFL4 cleared HT29-colorectal tumors using a single dose, whereas intratumoral injection cleared HT29-subcutaneous tumors within three doses. This approach addresses the limitations of other protein-based anticancer treatments by providing a non-invasive anticancer therapy with improved potency and tumor-specificity.
研究领域:
癌症治疗
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分子生物学
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药学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2023
·Vol. 191
·期 1
·1-10
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IF 5.7
Yue Yao,Ouyang Hezhong,Ma Mingyi,Yang Yaping,Zhang Haoda,He Aolin,Liu Ruijiang
A “turn-on” aptasensor for label-free and cell-free EpCAM detection was constructed by employing magnetic α-Fe 2 O 3 /Fe 3 O 4 @Au nanocomposites as a matrix for signal amplification and double-stranded complex (SH-DNA/Apt probes) immobilization through Au-S binding. α-Fe 2 O 3 /Fe 3 O 4 @Au could be efficiently assembled into uniform and stable self-assembly films via magnetic-induced self-assembly technique on a magnetic glassy carbon electrode (MGCE). The effectiveness of the platform for EpCAM detection was confirmed through differential pulse voltammetry (DPV). Under optimized conditions, the platform exhibited excellent specificity for EpCAM, and a strong linear correlation was observed between the current and the logarithm of EpCAM protein concentration in the range 1 pg/mL–1000 pg/mL ( R 2 = 0.9964), with a limit of detection (LOD) of 0.27 pg/mL. Furthermore, the developed platform demonstrated good stability during a 14-day storage test, with fluctuations remaining below 93.33% of the initial current value. Promising results were obtained when detecting EpCAM in spiked serum samples, suggesting its potential as a point-of-care (POC) testing. Graphical Abstract
研究领域:
生物化学
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医学诊断
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纳米技术
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Zichun Li,Yifan Liu,Feiran Liu,Guochen Sun,Xiaoling Zhang,Jing Jing
Background Exosomes, which are known to transport diverse proteins from parent cells to recipient cells, consequently influence the biological activities of the recipient cells. Among those proteins, the epithelial cell adhesion molecule (EpCAM), plays a crucial role as it is implicated in cell adhesion and signaling processes. As exosomal EpCAM potentially affects the migration of recipient cells, direct visualization with high spatial resolution is essential to better understand this impact and the role of exosomal EpCAM in recipient cells. Such understanding may provide valuable insights into the mechanisms underlying various diseases and potential treatment strategies. (94) Results This work focus on the selective labeling and fluorescent imaging of glycosylated EpCAM on tumor-derived exosomes using bioorthogonal click chemistry and aptamer-targeting strategies. To commence, exosomes with EpCAM overexpression, EpCAM N-glycosylation mutation, EpCAM silencing, or wildtype, were obtained by genetic manipulation. Subsequently, the glycosylation of exosomal EpCAM was directly visualized by capitalizing on the intramolecular fluorescence resonance energy transfer (FRET) that takes place between fluorescent EpCAM aptamers and fluorescent tags bound to glycans. As a result, this approach demonstrated its efficacy in investigating both the existence and the glycosylation state of exosomal EpCAM. Importantly, we proceeded to observe the uptake of tumor-derived exosomes by their recipient cells. It was then remarkably found that the expression and glycosylation levels of EpCAM in the co-cultured exosomes have a significant and substantial impact on the migratory ability of the recipient immune cells. (139) Significance We set up a novel labeling strategy for exosomal glycosylated EpCAM. This approach enabled us to realize the direct observation of exosomal EpCAM and its glycosylation with high spatial resolution. Based on this method, we find a significant role that the expression and the glycosylation of exosomal EpCAM in recipient cell adhesion. (52).
研究领域:
分子生物学
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细胞生物学
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癌症生物学
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生物化学
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免疫学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
TALANTA
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2022
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IF 6.556
Yaxue Dai,Yongjia Tang,Wenjing Huang,Yue Zhao,Xin Gao,Yueqing Gu
Breast cancer is a highly lethal and aggressive form of cancer. Early-stager diagnosis and intraoperative guidance are important endeavors for reducing associated morbidity and mortality among breast cancer patients. Epithelial cell adhesion molecule (EpCAM) is aberrantly expressed in the majority of breast carcinoma, making it an attractive imaging biomarker. Herein, we have designed novel EpCAM-targeting peptides (denoted as YQ-S) for precise breast carcinoma detection. The greater binding affinity of the designed peptide YQ-S2 over YQ-S1 and the reported peptide SNF was displayed on different cell lines with flow cytometry analysis, showing a positive correlation with the expression of EpCAM. Besides, YQ-S2 displayed an ideal biosafety profile with no evidence of any acute toxicity . Thus, YQ-S2 was chosen to represent YQ-S. By linking with the near-infrared fluorescent dye (MPA), we further developed the EpCAM-targeting probe (YQ-S2-MPA) for real-time imaging and fluorescence-guided resection of breast cancer tumors. In vivo imaging of the MCF-7 tumor-bearing model demonstrated higher tumor uptake of YQ-S2-MPA compared with that of SNF-MPA. The maximum tumor-to-normal tissue signal ratio of YQ-S2-MPA was 5.1, which was about 2 times that of SNF-MPA. Meanwhile, the metastatic lesions in 4T1 lung metastasis, and lymph node metastasis (LNM) mice were successfully detected under this imaging system. Notably, YQ-S2-MPA had excellent performance in surgical navigation studies in the preclinical models. Moreover, we exploited the 99m Tc-HYNIC-YQ-S2 to localize EpCAM positive tumors successfully. These data proved that YQ-S2 can distinguish EpCAM-positive orthotopic and metastatic tumors from surrounding normal tissues accurately, and possesses the clinical potential as a surgical navigation probe.
研究领域:
肿瘤学
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分子成像
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生物医学工程
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药学
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DOI
PubMed
高影响因子
TALANTA
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2025
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IF 6.1
Yi Yu,Wenhao Zhang,Qiyue Ding,Xiaolu Cheng,Kaiwei Wang,Guangxin Zhang,Boan Jiang,Xionghua Yu,Yu-Tao Li,Guo-Jun Zhang
Selectively and sensitively detecting specific exosomal markers is critical for early diagnosis of liver cancer. However, identifying specific exosomal biomarkers and establishing accurate, convenient detection methods remain challenging. In this study, we used bioinformatics to identify the higher levels of EpCAM and GPC-3 proteins on liver cancer exosomes. These markers were used to create a dual-antibody functionalized transistor biosensor for precise detection of liver cancer exosomes. The techniques exhibited outstanding specificity and sensitivity. Detection thresholds in PBS and simulated plasma were established at 20 particles/μL and 47 particles/μL, respectively, facilitating the distinction of liver cancer cell-derived exosomes from those originating from various other cancer cells. Furthermore, in clinical samples testing, this approach not only distinguished clinical samples among liver cancer patients and healthy individuals, but also demonstrated the ability to differentiate liver cancer from other types of tumors, achieving a precision and accuracy rate of 100 %. The developed biosensor demonstrates excellent potential for clinical application and this work offers a promising and effective approach for cancer diagnosis.
研究领域:
医学诊断
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生物信息学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Rong Qin,Mengqi Bai,Feiyi Zhang,Zengkai Wang,Fenglian Liu,Mingdong Dong,Lei Liu,Jian Xu
The detection of circulating tumor cells (CTCs) has emerged as a promising approach for the early diagnosis, therapeutic monitoring, and prognosis of malignant tumors. In this study, we present a novel magnetic nanoparticle (MP) functionalized with dual recognition peptides targeting the epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor 2 (HER2). Additionally, bovine serum albumin (BSA), an anti-fouling agent, is employed onto MP, effectively preventing the non-specific adhesion of platelets and proteins. This multifunctional peptide based magnetic biointerface (MPMB) platform effectively captures breast cancer cells in model systems and isolates CTCs from the blood of breast cancer patients. CTC enumeration of peripheral blood samples from 40 breast cancer patients, 30 benign breast tumor patients, and 30 healthy donors revealed a 70 % positivity rate in breast cancer patients (28/40), 6.7 % in benign breast tumor patients (2/30), and no positivity in healthy donors (0/30). CTC counts were significantly higher in breast cancer patients with advanced stages, particularly in those with distant metastasis, compared to early-stage patients ( p < 0.05). Moreover, among 10 breast cancer patients with positive CTC detection prior to surgery, 6 showed negative CTC results post-surgery. These findings indicate that the MPMB approach provides a simple, flexible, and efficient platform for monitoring therapeutic efficacy and evaluating prognosis in breast cancer patients undergoing treatment.
研究领域:
医学
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生物技术
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产品关联
DOI
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Mingzhu Zhao,Qin Li,Yan Zhao,Hanlin Zhou,Yuntian Yan,Rong-Mei Kong,Qingqing Tan,Weiheng Kong,Fengli Qu
Clinical diagnosis of ovarian cancer lacks high accuracy due to the weak selection of specific biomarkers along with the circumstance biomarkers localization. Clustering analysis of proteins transported on exosomes enables a more precise screening of effective biomarkers. Herein, through bioinformatics analysis of ovarian cancer and exosome proteomes, two coexpressed proteins, EpCAM and CD24, specifically enriched, were identified, together with the development of an as-derived dual-aptamer targeted exosome-based strategy for ovarian cancer screening. In brief, a DNA ternary polymer with aptamers targeting EpCAM and CD24 was designed to present a logic gate reaction upon recognizing ovarian cancer exosomes, triggering a rolling circle amplification chemiluminescent signal. A dynamic detection range of 6 orders of magnitude was achieved by quantifying exosomes. Moreover, for clinical samples, this strategy could accurately differentiate exosomes from healthy persons, other cancer patients, and ovarian cancer patients, enabling promising in situ detection. By accurately selecting biomarkers and constructing a dual-targeted exosomal protein detection strategy, the limitation of insufficient specificity of traditional protein markers was circumvented. This work contributed to the development of exosome-based prognosis monitoring in ovarian cancer through the identification of disease-specific exosome protein markers.
研究领域:
肿瘤学
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分子生物学
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诊断学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Pi Ding,Zhili Wang,Zeen Wu,Mingchao Hu,Weipei Zhu,Na Sun,Renjun Pei
The majority of current methods of isolating circulating tumor cells (CTCs) rely on a biomarker. However, the isolation efficiency may be compromised due to the heterogeneity of CTCs. In this work, a simple and broad-spectrum method is established to efficiently isolate the heterogeneous CTCs from patient blood samples using tannic acid (TA)-functionalized magnetic nanoparticles (MNPs). The TA-functionalized MNPs (MNPs-TA) inhibit the nonspecific adhesion of peripheral blood mononuclear cell (PBMC) and enhance cancer cell capture, resulting from the unique interaction between TA and glycocalyx on cancer cells. The MNPs-TA was demonstrated to effectively capture seven kinds of cancer cells (HeLa, PC-3, T24, MAD-MB-231, MCF-7, HT1080, A549) from artificial samples (62.3–93.7%). Moreover, this epithelial cell adhesion molecule (EpCAM)-independent CTC isolation method was also tested using clinical blood samples from patients with different cancers (21 patients), which may provide a universal tool to detect CTCs in the clinic.
研究领域:
纳米技术
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肿瘤学
·
生物医学工程
·
临床研究
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Yanqing Ran,Rui Dai,Xiaoshuo Zhang,Faqiong Zhao,Baizhao Zeng
Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein and its detection is important for diagnosis and therapeutic prognostic assessment of many cancers. Herein, a highly sensitive electrochemiluminescence (ECL) sensor was developed for its detection. In the ECL sensor, dimercaptosuccinic acid-capped core/shell structured CdTe/CdS quantum dot (QD) was loaded on metal-organic framework material UiO-66(Ce) as electrochemical luminophore; Ti 3 C 2 /Ag composite was introduced for immobilizing EpCAM aptamer. Due to the well immobilization of QD and catalysis of UiO-66(Ce), the obtained luminophore CdTe/CdS QDs@UiO-66(Ce) displayed a strong and stable ECL signal. Furthermore, the Ti 3 C 2 /Ag could act as a co-reactant accelerator to boost the ECL signal. Thus, the resulted sensor had quite strong initial ECL signal for signal-off detection. Further experiment showed that it exhibited good linear response to EpCAM over the concentration range of 1 pg mL −1 − 10 ng mL −1 in pH 7.4 Tris buffer, with a detection limit low to 0.66 pg mL −1 . Additionally, the ECL sensor also presented high selectivity and satisfying reproducibility; its practicability was demonstrated by the successful determination of EpCAM in serum samples.
研究领域:
分析化学
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生物化学
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癌症研究
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Sensors
·
2020
·
IF 7.333
Chenyun Wang,Cancan Wang,Dan Jin,Yi Yu,Fan Yang,Yulin Zhang,Qunfeng Yao,Guo-Jun Zhang
In this study, we report a gold nanoparticle (AuNP)-amplified surface acoustic wave (SAW) sensor for exosome detection with high sensitivity. The SAW chip was self-assembled with mercapto acetic acid to generate carboxylic groups via the Au–S bond. Anti-CD63 was then anchored onto the chip by pretreatment with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide,1-hydroxypyrrolidine-2,5-dione (NHS). Due to the existence of a membrane protein, CD63, on the exosome surface, exosomes could be bound onto the antibody-immobilized SAW chip. To amplify the detection signal, both the biotin-conjugated epithelial cell adhesion molecule (EpCAM) antibody as a secondary antibody and AuNP-labeled streptavidin were applied onto the exosome-bound SAW chip, resulting in AuNP assembly on the chip through biotin–avidin recognition. The sensor was capable of detecting 1.1 × 103 particles/mL exosomes, which was about 2 orders of magnitude higher than those detected by the strategy without using signal amplification. The sensor also achieved a satisfactory specificity and could detect the low-abundance exosomes directly in blood samples from cancer patients with minimal disturbance. This makes the SAW sensor useful for early diagnosis of cancer.
研究领域:
生物医学工程
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纳米技术
·
癌症诊断
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 10
·2483-2493
·
IF 6.331
Nanhang Zhu,Guohao Li,Juan Zhou,Yujia Zhang,Ke Kang,Binwu Ying,Qiangying Yi,Yao Wu
In vitro liquid biopsy based on exosomes offers promising opportunities for fast and reliable detection of lung cancers. In this work, we present a fluorescence resonance energy transfer (FRET) magnetic aptamer-sensor for magnetic enrichment of exosomes with aptamers and detection of cancerous-surface proteins based on a light-up FRET strategy. Fluorescent quantum dots (QDs) and aptamers were introduced onto magnetic nanoparticles and the fluorescence emission turned down when the aptamers were paired with their complementary DNA on the surface of Au nanoparticles. Later, competitive binding of exosomes with the aptamers expelled the Au nanoparticles resulting in an exosome concentration-dependent linear increase of QD fluorescence intensity in a broad exosome concentration range (5 × 102–5 × 109 particles per mL). As found in our work, this system behaved ultra-sensitively and the calculated detection limit of this FRET magnetic aptamer-sensor was as low as 13 particles per mL. Furthermore, taking epithelial cancer-specific antigen (epithelial cell adhesion molecule, EpCAM) screening as a typical example, our built FRET magnetic aptamer-sensor allowed a rapid and efficient distinction of all the epithelial cancer cases (7 lung cancers and 5 other cancers) from health volunteers with 100% accuracy.
研究领域:
生物医学工程
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分子诊断
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癌症研究
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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）