IEEE SENSORS JOURNAL
·
2026
·
IF 4.5
Lingling Fan,Cunhong Cen,Yuru Wu,Xiaohua Deng,Yuxuan Shi,Yuxing Huang,Xiaohong Tan,Shidong Li,Guiyin Li
Hepatocellular carcinoma (HCC) remains one of the most lethal malignancies worldwide, underscoring the urgent demand for early diagnostic strategies to improve patient survival rates. Glypican-3 (GPC3), a highly specific biomarker of HCC, has emerged as a promising target for early detection. Herein, we developed an innovative magnetic colorimetric aptasensor using ferrosoferric oxide@carbon quantum dots (Fe3O4@CQDs) nanocomposites. The Fe3O4@CQDs nanocomposites combine the magnetic properties of Fe3O4 with the unique optical characteristics of CQDs, exhibiting intrinsic peroxidase‑like activity. The animo-modified GPC3 aptamer (GPC3Apt) was covalently conjugated onto the Fe3O4@CQDs nanocomposites surface via EDC/NHS chemistry to form the recognition probe (Fe3O4@CQDs-GPC3Apt). Upon specific binding between the aptamer and GPC3, the resulting complexes (Fe3O4@CQDs-GPC3Apt-GPC3) modulate the catalytic oxidation of o-phenylenediamine (OPD) by H2O2, generating a yellow oxOPD product whose absorbance intensity correlated with GPC3 concentration. The proposed colorimetric aptasensor demonstrated a detection limit of 3.16 ng/mL and a linear range of 10–200 ng/mL, with high specificity against interfering proteins. It was successfully validated in human serum samples, yielding recoveries between 99.27% and 109.33%. Owing to its operational simplicity and cost‑effectiveness, this platform offers transformative potential for point-of-care HCC screening. Beyond advancing GPC3 detection, the work provides a flexible design paradigm that can be adapted for assays targeting other disease biomarkers.
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高影响因子
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2022
·Vol. 169
·期 8
·087517
·
IF 4.386
Shengnan Li,Xinhao Li,Liping Cao,Chaoxian Wang,Jintao Liang,Zhide Zhou,Guiyin Li
Glypican-3 (GPC3) is a serum marker for hepatocellular carcinoma (HCC) and has excellent specificity and sensitivity. Herein, the construction of an electrochemical aptasensor based on reduced graphene oxide-carboxymethyl chitosan-hemin-palladium nanoparticles (RGO-CMCS-Hemin/Pd NPs) and GPC3 aptamer (GPC3apt) has the function of GPC3 identification and analysis. RGO-CMCS-Hemin/Pd NPs has excellent biocompatibility, large specific surface area and good electrical conductivity, which is not only used as advanced sensing materials to modify the electrode surface to reduce the resistance and increase the signal amplitude, but also used as an electroactive substance to provide electrical signals. GPC3apt as a biometric element makes the aptasensor has good specificity and sensitivity. The GPC3apt can combine with GPC3 and form GPC3-aptamer conjugation, which increases the electron transfer impedance and changes the electrical signal. Under the optimum conditions, the aptasensor had a good linear relationship with the GPC3 concentration in the range of 1.0–100.0 ng ml−1 with R2 of 0.9573. The lower limit of detection was 1.0 ng ml−1. When the aptasensor was applied to GPC3 detection in human serum samples, the recovery was 93.73%–118.83%. In addition, the GPC3 aptasensor has excellent specificity, reproducibility and stability, which is anticipated to be applied for the clinical detection of GPC3.
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2021
·
IF 4.098
Huixue Wang,Jinya Liu,Wei Chen,Jintong Na,Yong Huang,Guiyin Li
Glypican-3 (GPC3), a heparin sulfate proteoglycan, is a potential diagnostic and therapeutic target for hepatocellular carcinoma. In this paper, a novel fluorescent aptasensor for GPC3 detection is constructed via [email protected] quantum dots–labeled GPC3 aptamer ( [email protected] Apt ) as a fluorescence probe. First, [email protected] is screened out with higher fluorescence intensity, which emits bright blue fluorescence under ultraviolet light. Then, the fluorescence-labeled [email protected] Apt probe is formed by the combination of amination GPC3 Apt and [email protected] using EDC/NHS coupled reaction. Under hydrogen bond and π-π interaction/stacking, the fluorescence of [email protected] Apt could be quenched by reductive graphene oxide (RGO) with the help of the photoinduced electron transfer and the fluorescence resonance energy transfer mechanism. In the presence of GPC3, the [email protected] Apt specifically recognizes and binds to GPC3, giving rise to the change of secondary structure of GPC3 Apt to form the GPC3/GPC3 Apt [email protected] complex, which would lead to the disintegration of the [email protected] Apt -RGO compound. Therefore, the energy transfer process is blocked and the fluorescence intensity is restored, enabling a highly sensitive response to GPC3. When the concentration of GPC3 is from 5.0 ng/mL to 150.0 ng/mL, the fluorescence recovery rate is well linearly related to GPC3 concentration with the limit of detection of 2.395 ng/mL (S/N = 3). This strategy shows recoveries from 98.31% to 101.89% in human serum samples and provides simple, fast and cheap analysis of GPC3, which suggests that it has great potential applications in clinical diagnosis for hepatocellular carcinoma.
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高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 5
·1-11
·
IF 6.232
Zhou Zhide,Zhao Le,Li Wenzhan,Chen Min,Feng Huafu,Shi Xiaohang,Liang Jintao,Li Guiyin
A Glypican-3 (GPC3) electrochemical aptamer nanobiosensor based on hemin/graphene nanohybrids (HGNs) peroxidase-like catalytic silver deposition and GPC3 aptamer has been constructed for the determination of GPC3. The HGNs were prepared by an one-step reduction method. Fourier transform infrared spectroscopy (FT-IR), ultraviolet spectroscopy (UV-vis), and transmission electron microscopy (TEM) were used to study the structure and morphological characteristics of the HGNs. The GPC3 electrochemical aptamer nanobiosensor was constructed using HGNs-aptamer (HGNs-Apt) as the signal probe and GPC3 aptamer as the capture probe. With the help of the catalytic action of peroxidase-like properties of HGNs, H 2 O 2 reduces the silver (Ag) ions in solution to metallic Ag, which deposit on the surface of the electrode. The amount of deposited Ag, which was derived from the amount of GPC3, was quantified by differential pulse voltammetry (DPV). Under optimal conditions, the current response of Ag had a good positive correlation with the GPC3 concentration in the range 10.0–100.0 μg mL −1 with a correlation coefficient of 0.9958. The detection limit was 3.16 μg mL −1 at a signal-to-noise ratio of 3, and the sensitivity was calculated to be 0.807 μA μM −1 cm −2 . The method is validated by analyzing spiked human serum samples with good recovery ranging from 101 to 122%. In addition, the GPC3 electrochemical aptamer nanobiosensor has acceptable selectivity, stability, and reproducibility.
A Glypican-3 electrochemical aptamer nanobiosensor based on hemin/graphene nanohybrids (HGNs) peroxidase-like catalytic silver deposition and GPC3 aptamer has been constructed for the determination of GPC3. The electrochemical aptamer nanobiosensor exhibits high selectivity, acceptance reproducibility, and good recovery performances.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Xue Zhang,Jiang Chen,Yuan Yin,Shijun Xiao,Rui Zhang,Haiyang Guo,Tong Yang,Tongyu Zhou,Siyan Zhang,Yang Yang,Caili Bi,Xiao-Jun Li
Targeted delivery of chemotherapeutic agents to the cancerous cells is of fundamental importance and the key step of the targeted delivery system design is to choice a specific receptor. Glypican-3 (GPC3) is a known cell membrane-associated oncofetal proteoglycan that is specifically up-regulated in the fast-growing hepatocarcinoma cells but rarely expressed in the normal healthy liver. Therefore, GPC3 may be a perfect targeting receptor for delivery treatment of hepatocellular carcinoma (HCC). In the present study, a GPC3 specific-targeting nanoliposomal drug delivery system was constructed with GPC3 targeting peptide (named as L5 peptide) modification and anticancer drug cantharidin encapsulation, which aims to realize cantharidin targeted treatment of liver cancer. In our study, nanoliposome specifically targeting GPC3 receptor was successfully constructed with particle size of 127.9 nm and a spherical shape. The targeted liposomes were stable under 4 °C or room temperature for almost 15 days. The drug release from L5-modified liposomes was controlled and delayed. Their targeted delivery properties were characterized by relatively more accumulation in the GPC3 highly expressed HepG2 cells than that of GPC3 lowly expressed Huh-7 cells. The competition results also indicated that the liposomes with L5 peptide modification could competitively bind to GPC3 receptor. Moreover, the liposomes showed colocalization with the lysosome after 3 h incubation. The L5-modified liposomal CTD had an augmented cell growth inhibition and tumor inhibition than that of the free CTD on HepG2 cells and GPC3 highly expressed tumor mice. Our study establishes a new strategy for improving HCC treatment and chemotherapeutic agent targeting delivery.
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高影响因子
BIOELECTROCHEMISTRY
·
2024
·
IF 4.8
Guiyin Li,Wenzhan Li,Yu Zhou,Xiaohong Tan,Qing Huang,Jintao Liang,Zhide Zhou
Glypican-3 (GPC3) is exclusively overexpressed in most Hepatocellular carcinoma (HCC) tissue but not in normal liver tissue, making it a promising biomarker for the precise detection of HCC. In this paper, a label-free light-addressable potentiometric sensor (LAPS) decorated by platinumpalladium-hemin-reduced graphene oxide nanocomposites (PtPd@H-rGO NCs) was constructed for determination of GPC3. The GPC3 aptamer (GPC3 Apt ) and PtPd@H-rGO NCs were modified on the surface of silicon-based LAPS chip to build sensitive unit of LAPS system. A readout photocurrent elicited from a modulated light source, registers the localized surface potential change. When a bias voltage is provided to the LAPS system, the GPC3-GPC3 Apt complexes formed by the specific reaction between GPC3 and GPC3 Apt at the sensing interface can cause the sensitive membrane surface potential to change, resulting in the photocurrent-voltage (I-V) curves generate a corresponding offset response. Therefore GPC3 concentration can be determined by monitoring the potential shifts (△V). Under optimal conditions, the potential shift is linearly related to the concentration of GPC3 in the range of 0.001–3.00 μg/mL with the limit of detection (LOD) of 0.0001 μg/mL. The LAPS has a good analytical performance with good specificity, reproducibility and stability, and can be used for the detection of GPC3 in actual serum samples, which provides a broad application prospect for the combined application of LAPS and aptamers in biooassay.
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高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 6
·1-16
·
IF 5.3
Li Guiyin,Guo Fei,Liang Jianlu,Wan Bingbing,Liang Jintao,Zhou Zhide
A new sandwich-type electrochemical biosensing platform was developed by gold @polyphthalenediamine nanohybrids (AuNP@PoPD) as the sensing platform and phosphorus doped reduced graphene oxide-hemin-palladium nanoparticles (PrGO-Hemin-PdNP) as the signal amplifier for phosphatidylinositol proteoglycan 3 (GPC3). AuNP@PoPD, co-electrodeposited into the screen printed electrode with high conductivity and stability, is dedicated to assembling the primary GPC3 aptamer (GPC3 Apt ). The second GPC3 Apt immobilized on the high conductivity and large surface area of PrGO-Hemin-PdNP was utilized as an electrochemical signal reporter by hemin oxidation (PrGO-Hemin-PdNP-GPC3 Apt ). In the range 0.001–10.0 ng/mL, the hemin oxidation current signal of the electrochemical aptasensor increased log-linearly with the concentration of GPC3, the lowest detection limit was 0.13 pg/mL, and the sensitivity was 2.073 μA/μM/cm 2 . The aptasensor exhibited good sensing performance in a human serum sample with the relative error of 4.31–8.07%. The sandwich sensor showed good selectivity and stability for detection GPC3 in human serum samples, providing a new efficient and sensitive method for detecting HCC markers. Graphical Abstract
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高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Liu Jinhu,Zhao Huajun,Gao Tong,Huang Xinyan,Liu Shujun,Liu Meichen,Mu Weiwei,Liang Shuang,Fu Shunli,Yuan Shijun,Yang Qinglin,Gu Panpan,Li Nan,Ma Qingping,Liu Jie,Zhang Xinke,Zhang Na,Liu Yongjun
Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment.
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高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Weiwei Mu,Dandan Jiang,Shengjun Mu,Shuang Liang,Yongjun Liu,Na Zhang
The specific-targeting approach could promote the specificity of diagnosis and the accuracy of cancer treatment. The choice of a specific-targeting receptor is the key step in this approach. Glypican-3 (GPC3) is an oncofetal proteoglycan anchored on the cell membrane. It is overexpressed even in the early stage of hepatocellular carcinoma (HCC), whereas it shows almost no expression in the healthy adult liver. Therefore, GPC3 may be applied as a specific-targeting receptor for HCC theranostics. In this study, a GPC3 specific-targeting theranostics nanodevice, GPC3 targeting peptide (named G12)-modified liposomes co-loaded with sorafenib (SF) and IR780 iodide (IR780), was developed (GSI-Lip), which aims to realize early diagnosis and precise chemo-photothermal therapy of HCC. SF was the first-line chemotherapy drug for the treatment of HCC. IR780 was used for photothermal therapy and near-infrared fluorescence imaging. The evaluation of early diagnosis verified that early-stage tumors (3.45 ± 0.98 mm3, 2 days after 5 × 105 H22 cells’ inoculation in mice) could be clearly detected using GSI-Lip, which was significantly more sensitive than folic acid-modified liposomes (p < 0.01, 32.90 ± 10.01 mm3, 4 days after 1 × 106 H22 cells’ inoculation in mice). The study of the endocytic pathway indicated that specific G12/GPC3 recognition may induce caveolae-mediated endocytosis of GSI-Lip. Notably, the accumulation of GSI-Lip in tumors was significantly increased compared with that observed with folic acid-modified liposomes (p < 0.01). Specific-targeting endowed the precise antitumor effect of GSI-Lip. GSI-Lip showed a higher antitumor efficacy in comparison with folic acid-modified liposomes (inhibition rate: 90.52% vs 84.22%, respectively; p < 0.01). During a period of 21 days, the synergistic chemo-photothermal therapy (GSI-Lip + laser) exhibited a better antitumor effect versus GSI-Lip without laser (inhibition rate: 94.93% vs 90.52%, respectively; p < 0.01). Overall, GPC3-targeted GSI-Lip promoted the sensitivity and specificity of HCC early diagnosis and achieved synergistic efficacy of chemo-photothermal theranostics, which has potential clinical applications. Furthermore, the present study revealed that a more specific-targeting ligand could further improve the efficacy of theranostics against HCC.
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高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 19
·8608-8618
·
IF 3.591
Min Chen,Haimei Li,Xueming Su,Runqiang Wu,Huafu Feng,Xiaohang Shi,Jintao Liang,Jiejing Chen,Guiyin Li
Glypican-3 (GPC3) is a potential hepatocellular carcinoma (HCC) serum marker with good sensitivity and specificity. Herein, a label-free electrochemical aptasensor for the detection of GPC3 was developed using a reduced graphene oxide–hemin–chitosan (RGO–H–CS) nanocomposite-modified screen-printed electrode (SPE) as a biosensing platform and GPC3 aptamer as the recognition element. When GPC3 was present, the aptamer could specifically bind with the target GPC3 by specific recognition reaction and form GPC3–aptamer conjugations on the sensing surface, which could alter the electrochemical redox signal of hemin (Fe(III)/hemin(Fe(II))) in the RGO–H–CS nanocomposite recorded by differential pulse voltammetry (DPV). The electrochemical GPC3 aptasensor was characterized via scanning electron microscopy (SEM), Raman spectroscopy, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under optimal conditions, currents originating from the oxidation of hemin had a linear relationship with the concentration of GPC3 in the range of 0.01 µg mL−1 to 10.0 µg mL−1 with a detection limit of 7.9 ng mL−1 (S/N = 3). The developed aptasensor was applied to detect the GPC3 level in the human serum samples with the recovery rate of 101.04–104.9%. Moreover, the label-free aptasensor exhibited considerable anti-interfering ability, acceptable stability and good reproducibility. Therefore, this study provides a reliable and objective analysis method to achieve high screening for the early diagnosis of HCC.
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高影响因子
BIOELECTROCHEMISTRY
·
2025
·
IF 4.5
Xuyang Chen,Lingling Fan,Kaipeng Su,Shuwei Wen,Xiaohong Tan,Yuge Liu,Xiaohua Deng,Xiangming Li,Yong Huang,Guiyin Li
Hepatocellular carcinoma (HCC) is a high-mortality malignancy that urgently requires sensitive early-stage biomarkers. Glypican-3 (GPC3), a highly specific protein biomarker for HCC, calls for efficient detection strategies. Herein, we developed a label-free electrochemical aptasensor based on nitrogen-doped reduced graphene oxide-ferrocene-polyaniline (NRGO-Fc-PANI) nanocomposites and GPC3 aptamer for GPC3 detection. The NRGO-Fc-PANI combined the large high surface area and conductivity of NRGO, high electrical conductivity and stability of PANI, and the good redox properties of Fc, which functed as in situ electrochemical redox signal indicator to monitor the electrochemical changes. Upon target binding, the formation of GPC3-aptamer complex fell off from the electrode, exposing the conductive NRGO-Fc-PANI layer and enhancing the differential pulse voltammetry (DPV) response. The aptasensor exhibited a linear detection range of 10.0–100.0 ng·mL −1 (R 2 = 0.996) and a low limit of detection (LOD) of 2.88 ng·mL −1 . It demonstrated excellent selectivity toward interfering proteins, retained 70.8 % of its initial signal after 11 days of storage, and attained a recovery range of 97.0–109.5 % in human serum samples. By eliminating the need for enzymatic or fluorescent reporters, the aptasensor reduced reagent costs and operational complexity, presenting a clinically promising tool for the early diagnosis of HCC.
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高影响因子
BIOELECTROCHEMISTRY
·
2020
·
IF 4.722
Guiyin Li,Huafu Feng,Xiaohang Shi,Min Chen,Jintao Liang,Zhide Zhou
Glypican-3 (GPC3) is a highly specific tumor marker for hepatocellular carcinoma (HCC), and plays an important role in reflecting the existence, therapeutic evaluation, monitoring and prognosis of HCC. Herein, an electrochemical aptasensor was designed for GPC3 detection with the reduced graphene oxide-hemin nanocomposites (RGO-Hemin) modified on the screen-printed electrode surface as the sensing platform and GPC3 aptamer as recognize molecule. In the existence of GPC3, the aptamer can specifically bind with the target GPC3 and form GPC3-aptamer conjugations on the sensing surface, which would increase the resistance of the electron transfer on the electrode and make the decrease of electrochemical signals of Hemin in RGO-Hemin nanocomposites. The electrochemical current change was recorded by differential pulse voltammetry (DPV). Scanning electron microscopy (SEM), Raman microscope (RM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to characterize the GPC3 electrochemical aptasensor. Under the optimum conditions, the current response of the electrochemical aptasensor is linearly correlated with the concentration of GPC3 (0.001–10.0 μg/mL) with the detection limit of 2.86 ng/mL (S/N = 3) and the sensitivity of 0.134 μA/μM/cm 2 . In addition, the aptasensor was applied to the determination of GPC3 in spiked human plasma and the recoveries fluctuated from 102.68% to 117.29%. All these results show that the aptasensor has good specificity, sensitivity, stability and reproducibility for GPC3 detection.
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高影响因子
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