ANALYTICA CHIMICA ACTA
·
2026
·
IF 6.1
Pengxiao Guo,Jianshe Li,Huijing Du,Kanglei Wang,Lei Zhang,Shuguang Li
Traditional surface plasmon resonance (SPR) sensors generally rely on a single sensing interface, making it difficult to achieve selective enhancement of different response mechanisms, thereby limiting their multiparameter detection capability and sensing performance. In this work, a multi-mechanism signal amplification SPR fiber-optic sensing platform based on interface-cooperative regulation is proposed for the simultaneous detection of epidermal growth factor receptor (EGFR) exon 20, pH, and temperature, while enabling real-time temperature compensation. By constructing functional interfaces with distinct physicochemical characteristics, synergistic signal amplification through multiple sensing mechanisms is achieved. Specifically, the Ag interface utilizes stable Ag–S bonding to enable efficient immobilization of probe DNA for the specific recognition of exon 20; the hydroxyl-rich Ag/TiO 2 interface facilitates the stable assembly of the PAA/CS functional layer to form a pH-responsive channel; and the Ag/MoS 2 /PDMS composite structure provides temperature monitoring and compensation through its thermosensitive characteristics. Meanwhile, the synergistic optical regulation of the high-refractive-index TiO 2 layer and the two-dimensional MoS 2 material enhances the local electromagnetic field and enables effective spectral separation among multiple sensing channels, resulting in improved sensing performance. Experimental results demonstrate average sensitivities of 0.178 nm/nM, −22.59 nm/pH, and −4.439 nm/°C for exon 20, pH, and temperature detection, respectively. By introducing a real-time temperature compensation strategy, the accuracy and reliability of EGFR exon 20 detection are further improved. The proposed sensing platform provides a promising approach for lung cancer biomarker analysis and multimodal physiological monitoring in complex biological environments.
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高影响因子
APOPTOSIS
·
2025
·
IF 8.1
Huang Xiangyang,Liu Yi,Fu Hangling,Rong Xia,Zhao Yiheng
Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by progressive skin and organ fibrosis. Although interferon signaling is dysregulated in SSc, the role of interferon-induced proteins like IFIT3 in the skin fibrosis of SSC remains unclear. Here, we demonstrate that IFIT3 expression is significantly elevated ( p < 0.01) in SSc fibroblasts and promotes fibrosis via SOCS1-dependent activation of the EGFR/VEGF axis. Silencing IFIT3 upregulated SOCS1 ( p < 0.05), suppressed EGFR/VEGF ( p < 0.01), and inhibited fibroblast proliferation/migration ( p < 0.01). In a bleomycin-induced SSc model, IFIT3 knockdown ameliorated skin/lung collagen deposition and fibrosis ( p < 0.05). Our findings reveal a novel mechanism whereby IFIT3 regulates EGFR and VEGF through down-regulating SOCS1 in SSc fibrosis, identifying IFIT3 as a novel therapeutic target for SSc.
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Wenjing Lu,Fangfang Du,Xuewei Zhao,Lihong Shi,Shaomin Shuang,Xinyan Tracy Cui,Chuan Dong
Because of the demand for precision medicine, the investigatation on the application of carbon-dots-based nanosystems in the field of biomedicine is attracting more and more attention. Therefore, we have built a multifunctional nanosystem based on sulforaphane-conjugated carbon dots (SFN-CDs) with thiourea skeleton and applied for EGFR-overexpressing cancer cells targeted imaging and inhibiting. The SFN-CDs are formed by grafting sulforaphane on the amino-rich yellow fluorescent carbon dots, which have excellent optical stability and can be distinguished from normal cells for targeted imaging of cancer cells. The vitro toxicity experiments demonstrated that the SFN-CDs can effectively inhibit EGFR-overexpressing cancer cell proliferation at concentrations below 100 μg mL–1. All these results validated that SFN-CDs nanoparticles with integration of diagnostic and therapeutic functions can be used as a potential nanodurg in early stage of cancer control. Moreover, this work provides useful insight into targeted nanoparticle design in the biological nanomedicine field.
研究领域:
纳米医学
·
癌症诊疗一体化
·
生物医学成像
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分子靶向治疗
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生物偶联化学
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高影响因子
Antioxidants
·
2026
·Vol. 15
·期 8
·984
·
IF 8.2
Mengjiao She,Ao Yu,Xiaozhan Qiu,Wanyu Liu,Rui Chen,Renshan Deng,Huan Zeng,Chunling Zhu,Qiong Wu,Jinlan Meng,Wenjie Mei
The urgent need for novel glioblastoma (GBM) therapies has motivated the exploration of EGFR G-quadruplex (G4) targeting, which suppresses oncogene transcription independently of kinase activity. However, existing EGFR G4 ligands lack subtype selectivity. Through computer-aided design and systematic bioisosteric modifications of the 1H-imidazo[4,5-f][1,10]phenanthroline scaffold, we synthesized a series of derivatives. We evaluated their G4 interactions by molecular docking, UV-Vis, FRET, ITC, and CD. Compound3, bearing a 6-bromopiperonyl group, exhibited nanomolar affinity for EGFR G4 (Kd = 102 nM) with ~146-fold selectivity over K-Ras G4, stabilizing it via end-stacking. It potently inhibited U87-MG glioblastoma cell proliferation (IC50= 0.49 μM), with a wide safety margin relative to normal HMC3 microglia (safety index = 14.18). Mechanistically, compound3triggered DNA damage, mitochondrial oxidative stress, and sequential multi-organelle damage to mitochondria, lysosomes, and the endoplasmic reticulum, while impairing cell migration and invasion. These findings establish compound3as a uniquely selective EGFR G4 stabilizer, offering a promising multi-organelle-damage strategy for glioblastoma therapy.
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高影响因子
Oncotarget
·
2017
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IF 5.168
Zhe Cheng,Ling-Ling Dai,Xi Wang,Liu-Qun Jia,Xiao-Gang Jing,Peng-Fei Li,Meng Liu,Huan Wang,Lin An
This study aims to explore how microRNA-145 (miR-145) affects airway remodeling and cytokine expression by targeting epidermal growth factor receptor (EGFR) to regulate mucin 5AC (MUC5AC). Mice alveolar epithelial cells (AECs) were divided into a control, blank, miR-145 mimics, mimic control, miR-145 inhibitors, inhibitor control, si- EGFR and miR-145 inhibitors + si- EGFR group. Asthma mice models with airway remodeling were induced with an Ovalbumin (OVA) solution and randomly divided into a normal, asthma, asthma + miR-145 mimics, asthma + miR-145 mimic control, asthma + si- EGFR or asthma + si- EGFR NC group. Airway remodeling degree and histomorphology was measured using hematoxylin-eosin (HE), Masson and periodic acid-Schiff (PAS) staining. Flow cytometry was used to detect Th2 and Th17 cells in peripheral blood, ELISA was used to measure inflammatory factors. qRT-PCR and western blotting was adapted to detect the expressions of EGFR and the relevant cytokines that are regulated by miR-145. The control, miR-145 mimics and si- EGFR groups showed a higher expression of miR-145 and a lower expression of EGFR and cytokines than the blank, mimic control, inhibitor control and miR-145 inhibitor + si- EGFR groups. Mice in the asthma + miR-145 mimics and asthma + si- EGFR groups showed lower WAt/Pbm, WAi/Pbm and WAm/Pbm, less inflammatory cells, less airway modeling and alleviated goblet cell hyperplasia and mucus obstruction than the asthma group. Furthermore, the expressions of EGFR and cytokines of transfected cells and lung tissues were negatively related to those of miR-145. MiR-145 can down-regulate MUC5AC by negatively targeting EGFR and thereby relieving airway remodeling.
研究领域:
分子生物学
·
呼吸医学
·
免疫学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zehan Zeng,Mingzhen Zhong,Tong Liao,Xuan Zhou,Lin Shi,Xin Zhang,Ye Zhang,Jingyan Feng,Yiqian Chen,Shuya Sheng,Jun Chen,Lei Zheng,Weilun Pan,Jinxiang Chen
Plasma extracellular vesicles (EVs) have emerged as promising biomarkers for the early diagnosis of glioblastoma. However, rapid and efficient isolation and detection of tumor-specific EV subsets from plasma remains challenging. To address this, we developed an innovative integrated chip based on self-sacrificial metal–organic frameworks and the epidermal growth factor receptor (EGFR) aptamers called ZIF-8@EGFR aptamer (ZIF-8@Apt), which further coupled with a “nano-fuels”-driven DNAzyme amplification strategy. The core functionality of the constructed chip lies in its ability to capture EVs with the ZIF-8@Apt module. Once captured, numerous DNA “nano-fuel” structures are in situ assembled on the EVs’ surfaces. Subsequently, the ZIF-8@Apt@EV@nano-fuels composites are lysed to release Zn 2+ , the EVs’ nucleic acids, and additional nano-fuels for subsequent detection. Finally, a DNAzyme detection system is introduced, where the released nano-fuels activate the DNAzyme, leading to multiple signal amplification aided by Zn 2+ for highly sensitive detection of plasma EVs. This integrated approach effectively enriches and detects target EVs, achieving a significantly enhanced detection sensitivity of 500 particles/μL. In a clinical study involving glioblastoma patients, our chip demonstrated a remarkable ability to distinguish between cancer patients and healthy individuals, achieving an area under the curve (AUC) of 0.958. Moreover, the response signals of the chip can be conveniently read using fluorescence spectroscopy or microscope, offering a rapid, highly sensitive, and high-throughput analysis of plasma EVs for various application scenarios. Overall, this study introduces a comprehensive approach for the rapid isolation and accurate analysis of plasma EVs, holding significant promise for early diagnosis and disease monitoring.
研究领域:
生物医学工程
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分子诊断
·
癌症研究
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DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Zenghui Liu,Hesen Wang,Jinge Li,Mengli Wang,Huaixia Yang,Fuchun Si,Jinming Kong
As a new serum biomarker, the sensitive detection of exosomes is significant for the early diagnosis of diseases. In this paper, a novel electrochemical biosensor for the sensitive detection of exosomes was constructed utilizing a novel C 60 hybrid as a tracer. Firstly, the epidermal growth factor receptor (EGFR) antibody was immobilized on the electrode surface via Au-NH 2 bonding with Nafion AuNPs substrate. After specific capture of exosomes, C 60 -Au-Tb was grafted onto the surface of exosomes through “carboxyl-Zr 4+ -phosphate” chemistry, causing a change in the current signal. Under the optimal conditions, there was a linear relationship between the SWV signal and the logarithm of exosomes concentration from 5 × 10 4 exosomes/mL to 5 × 10 9 exosomes/mL, and the detection limit was 2.67 × 10 4 exosomes/mL. In addition, the biosensor had the advantages of high specificity, strong anti-interference ability, good repeatability, and stability. In conclusion, this method had great potential in diagnosing early cancers associated with exosomes.
研究领域:
生物传感器
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分析化学
·
癌症诊断
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Yu Chen,Jie Mei,Ping Zhang,Jiayu Liu,Lingyan Chen,Liwei Wu,Yan Zhang
IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein to transduce multiple signals from the extracellular microenvironment. However, whether IQGAP1 mediates EGF-induced cancer progression has been not observed. In this research, we explored the immunological correlations of IQGAP1. IQGAP1 was up-regulated in most cancer and related to poor prognosis in ovarian cancer. In addition, IQGAP1 was correlated with immune-related genes and tumor-infiltrating lymphocytes. IQGAP1 was a novel EGF-response gene, which was up-regulated by EGF. As the downstream of EGFR, IQGAP1 mediated EGF-induced proliferation, migration and invasion of tumor cells and was essential for EGF-induced PD-L1 expression as well. Mechanically, IQGAP1 interacted with STATs and mediated their phosphorylation. Furthermore, Curcumin inhibited EGFR/IQGAP1 axis to down-regulate PD-L1 and suppress cancer progression. To sum up, IQGAP1 responds to EGF stimulation and mediates EGF-induced phosphorylation of STATs, which is a novel promising target for blocking the EGF-induced cancer progression.
研究领域:
癌症生物学
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免疫学
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分子生物学
·
细胞信号传导
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Ming Li,Junhu Zhao,Meiyan Liao,Heng Zheng,Fei Cheng,Youhang Zhang,Hanfei Zhang,Pier-Luc Tremblay,Tian Zhang
The accurate detection of circulating tumor DNA (ctDNA) in patients’ biological fluids can facilitate cancer diagnosis and prognosis. This study reports the development of a differential pulse voltammetric (DPV) biosensor for the detection of ctDNA coding for the key T790M lung cancer mutation of the epidermal growth factor receptor (EGFR). The biosensor was built with a working electrode (WE) made of optimized electroconductive particles comprising covalent organic frameworks (COF) displaying Au nanoparticles (Au NPs) modified with polyethyleneimine (COF@Au-PEI). Au NPs accelerated electron transfer while COFs and PEI maximized the architecture of the WE to improve electrochemical reactions and molecular probe binding. Next, hairpin DNA probes (haiDNA) specific to the EGFR T790M ctDNA analyte were bonded to COF@Au-PEI. Lastly, Au@Pt nanohybrids were attached to the WE to enhance its electrochemical performance. In this system, the long polynucleotide EGFR T790M ctDNA analyte interferes with electrochemical reactions upon binding to the haiDNA probes, resulting in a proportional decrease of the DPV signal. The device detected EGFR T790M ctDNA in blood plasma and exhibited good sensitivity, accuracy, stability, and reproducibility. The sensor was also highly selective with no DPV signal for the EGFR wildtype allele harboring a difference of only one base pair.
研究领域:
生物传感器技术
·
癌症诊断
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分子生物学
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纳米材料科学
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DOI
高影响因子
Materials Express
·
2021
·Vol. 11
·期 10
·1619-1627
·
IF 0
Zhang Yue,Liu Yuanfen,Hu Yumin,Pan Lei
In this study, we developed an active targeting nano-immunoplatform of doxorubicin (DOX)-loaded bovine serum albumin (BSA) modified with the humanized antibody cetuximab, which can target the epidermal growth factor receptor (EGFR) of EGFR-overexpressing colon cancer, and subjected
it to a series of in vitro evaluation. The obtained cetuximab-modified nanoparticles (cetuximab-DOX-immuno-NPs) had an average particle size of 218.2±2.2 nm, a polydispersity index of 0.162±0.023, a zeta potential of −23.28±0.75 mV, and a cetuximabloading
efficiency of 33.6%±3.5%. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity experiments showed that the cytotoxic of cetuximab-DOX-immuno-NPs in EGFR-overexpressing RKO colon cancer cells was significantly higher than it was in EGFR-under-expressing
LS174 T cells. The results of flow cytometry showed that when DOX-immuno-NPs were used, DOX was eliminated soon after entering the cells, whereas when cetuximab-DOX-immuno-NPs were used, DOX efflux was reduced. Confocal laser-scanning microscopy was used to visualize the endocytosis of nanoparticles,
and revealed that the fluorescence intensity of cetuximab-DOX-immuno-NPs was significantly higher than that of non-specific IgG-DOX-immuno-NPs in RKO cells. Moreover, in EGFR-under-expressing LS174 T cells, both cetuximab-DOXimmuno-NPs and Immunoglobulin G-DOX-immuno-NPs showed weak DOX fluorescence
intensity, reflecting the specificity and selectivity of cetuximab-modified nanoparticles toward EGFR-overexpressing cancer cells. This study demonstrated that cetuximab modification of DOX-loaded BSA nanoparticles can increase their selectivity and reduce their toxicity. As this would decrease
the side effects of these treatments in patients, this study shows that cetuximab-modified doxorubicin-loaded bovine serum albumin nanoparticles are promising candidates for targeted colon cancer therapy.
研究领域:
药学
·
肿瘤学
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生物医学工程
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DOI
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 7
·1917-1927
·
IF 4.157
Zhang Liyang,Yi Xinyao,Wang Saisai,Liang Peida,Zhou Huaxin,Fu Jia,Jia Qianqian,Gao Jiapan,Lv Yanni,Han Shengli
A novel stability-enhanced graphene quantum dot (GQD)-decorated epidermal growth factor receptor (EGFR) cell membrane chromatography was constructed to study the potential application of GQDs in bioaffinity chromatography, and to screen active components acting on EGFR from traditional Chinese medicine (TCM). The carboxyl groups on the surface of GQDs reacted with the amino groups of the amino-silica gel ( SiO 2 -NH 2 ) to form a covalent bond, thereby preparing the GQD-decorated silica gel ( SiO 2 -GQDs ). The EGFR cell membrane was further immobilized on the SiO 2 -GQDs through the same covalent binding method to obtain the GQD-decorated cell membrane stationary phase ( SiO 2 -GQDs-CMSP ). In this way, the cell membrane was firmly immobilized on the decorated silica carrier. The life span and stability of the GQD-decorated cell membrane chromatographic ( SiO 2 -GQDs-CMC ) column were both enhanced, and the optimal immobilization conditions of the EGFR cell membrane were also determined. This model was then verified by establishing a SiO 2 -GQDs-CMC online liquid chromatography-ion trap-time-of-flight (LC-IT-TOF) system to screen possible active components in Peucedanum praeruptorum Dunn . As a result, praeruptorin B (Pra-B) was screened out, and its inhibitory effect against EGFR cell growth was evaluated by the cell counting kit-8 (CCK-8) assay. Molecular docking assay was also conducted to further estimate the interaction between Pra-B and EGFR. Overall, this research indicated that GQDs may be a promising nanomaterial to be used in prolonging the life span of the CMC column, and Pra-B could be a potential EGFR inhibitor so as to treat cancer. Graphical abstract
研究领域:
分析化学
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药理学
·
纳米生物学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Yuying Wang,Quanwei Yu,Xiongqi Yang,Lingling Ma,Ridong Huang,Hai Chen,Zhonghua Jiang,Zhenru Wu,Chengyong Wu,Xuemei Deng,Jing Wang,Weimin Li,Yang He
The tertiary C797S mutation in the EGFR tyrosine kinase domain disrupts osimertinib binding, driving resistance in NSCLC. We designed a series of novel diaminopyrimidine derivatives to establish the interaction with Ser797. H8b potently inhibited EGFRL858R/T790M/C797S kinase with an IC50 of 3.86 nM (30-fold lower than osimertinib) and suppressed both double mutant NCI-H1975 and triple mutant H1975-M3 cells with IC50s of 0.03 μM and 0.57 μM (14- and 11-fold reductions over osimertinib, respectively). Cocrystal X-ray analysis revealed that H8b forms a “two-point tethering” in the ATP pocket with a hydrogen bond between its dichloropropionamide oxygen and Ser797, complemented by a hydrogen bond between terminal N of the piperazine ring and Phe795. Mechanistically, H8b suppressed EGFR phosphorylation and downstream AKT, STAT3, and MAPK signaling, inhibiting proliferation, invasion, and migration. In vivo, H8b achieved 71.15% tumor inhibition in H1975-M3 xenografts. This study identifies H8b as a promising EGFR-TKI overcoming C797S-mediated resistance.
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高影响因子