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.
研究领域:
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
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.
研究领域:
肿瘤学
·
分子生物学
·
药剂学
✓ 已验证
DOI
PubMed
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
研究领域:
生物医学工程
·
分析化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
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.
研究领域:
生物化学
·
分子诊断
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Xiaohong Tan,Wenzhan Li,Wei He,Tingting Yu,Bingbing Wan,Yong Huang,Jintao Liang,Guiyin Li
Glypican-3 (GPC3), which is a surface heparan sulfate proteoglycan, has been widely known the ideal biomarker for diagnosis and treatment of hepatocellular carcinoma (HCC). Accurate and sensitive detection of serum GPC3 level is an important and challenging task. In this paper, a sandwich electrochemical aptasensor was designed to specifically detect serum GPC3 level through aptamer-target-aptamer recognition. A GPC3 aptamer (GPC3 Apt ) immobilized on the surface of gold nanoparticles@reduced graphene oxide modified screen-printed electrode (Au NPs@rGO/SPCE) was used as the capture probe. Hemin-reduced graphene oxide-carboxymethyl chitosan@platinum nanoparticles (H-rGO-CMC@Pt NPs), with good mimicking peroxidases activity, were labeled with amination GPC3 aptamer, which was employed as the signal probe. Once the target GPC3 was anchored on the surface of GPC3 Apt /Au NPs@rGO/SPCE, the H-rGO-CMC@Pt NPs-GPC3 Apt was further specifically bound to the GPC3, forming the aptamer-target-aptamer sandwich structure, which can catalyze the oxidation of hydroquinone (HQ) to benzoquinone (BQ) and lead the oxidation current of HQ recorded by DPV to changing. The linear relationship between the current signal of oxidation of HQ and GPC3 concentration range of 0.0001–3.0 µg/mL and 3.0–60.0 µg/mL, with a low detection limit (LOD) of 0.0685 ng/mL. Additionally, the electrochemical aptasensor was successfully applied for the detection of GPC3 in human serum samples with the recovery of 99.95–104.06 % and relative standard deviation (RSD) of 1.31–5.22 %. Thus, the sandwich aptasensor could provide a new strategy for detection of serum GPC3 level and improve the early diagnosis rate of HCC.
研究领域:
生物医学工程
·
肿瘤学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2021
·Vol. 17
·期 4
·677-690
·
IF 4.099
Zhou Shuping,Ma Yongfang,Liu Xueke,Yu Pan,Huang Ning,Song Li,Xu Ruyue,Huo Zhen,Zhu Tao,Tang Xiaolong
The miR let-7b-5p (a kind of microRNAs) has many pathophysiological regulation effects, including human hepatocellular carcinoma (HCC) pathogenesis. This study investigated whether nanoparticle-mediated miR let-7b-5p could jointly enhance the therapeutic effect of sorafenib on HCC by
inhibiting the proliferation of HCC cells, inducing apoptosis, and reversing drug resistance. We evaluated the level of miR let-7b-5p in sorafenib-resistant HepG2 cells (HepG2R) and HepG2 HCC cells by qRT-PCR and analyzed the biological effects of hepatocellular carcinoma treated
with sorafenib with miR let-7b-5p, and further studied the toxicity of nanoparticles (Ab-miR-NPs) that deliver miR let-7b-5p mimics and target GPC3 on the surface of hepatocellular carcinoma cells. Results showed that, in HepG2 cells, the expression level of miR let-7b-5p was significantly
higher than that in HepG2R cells. Targeted nanoparticle Ab-miR-NPs mediated the delivery of miR let-7b-5p to the HCC cytoplasm and released miRNA after being broken down, down-regulating the expression of IGF1R and inhibiting AKT/mTOR and Ras/Raf signal transmission. Ab-miR-NPs
not only enhanced the proliferation of sorafenib in cultured HepG2R cells and induced cell apoptosis efficiency, but they also improved the anti-tumor activity in the mouse models. These results indicated that GPC3 antibody-modified PLGA-PLL (polylactic acid-glycolic acetic copolymer
grafted hyper-branched polylysine) loaded miR let-7b-5p polymer nanoparticles combined with sorafenib may be a new treatment strategy for HCC resistant to sorafenib.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
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.
研究领域:
生物医学工程
·
分子诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 23
·6804-6817
·
IF 7.59
Guiyin Li,Wenzhan Li,Shengnan Li,Xinhao Li,Xiaoqing Yao,Wen Xue,Jintao Liang,Jiejing Chen,Zhide Zhou
Glypican-3 (GPC3) is a membrane-associated proteoglycan that is specifically upregulated in hepatocellular carcinoma (HCC) and has become one of the most promising biomarkers closely related to the occurrence and development of HCC. In this work, platinum@palladium nanoparticles decorated with hemin-reduced graphene oxide (H-rGO-Pt@Pd NPs) were used not only as a support for GPC3 aptamer (GPC3Apt) immobilization, but also as a new redox nanoprobe in electrochemical analysis for the determination of GPC3. The electrochemical aptasensor involved a reaction cell with a three-electrode system, and the differential pulse voltammetry (DPV) technique was adopted. In the presence of GPC3, the formed GPC3Apt–GPC3 complexes had stable structures and were cleaved from the electrode surface, leading to more electroactive H-rGO-Pt@Pd NPs repelling freely from the GPC3Apt/H-rGO-Pt@Pd NPs and thus to the increase of the oxidation peak current of hemin in H-rGO-Pt@Pd NPs. Under optimal conditions and a working voltage of +700 mV (vs. Ag/AgCl), the label-free electrochemical GPC3 aptasensor showed superior performance with a wider concentration linear range (0.001–10.0 μg mL−1), a lower limit of detection (LOD) (0.181 ng mL−1, S/N = 3), a higher sensitivity (0.0446 μA μM−1 cm−2) and good selectivity. Furthermore, the fabricated aptasensor was applied to GPC3 determination in human serum samples with satisfactory recoveries of 94.3%–119% and RSDs of 0.15%–5.78%. The current work provides a flexible approach for the rapid and sensitive analysis of GPC3 and has a broad application prospect in the diagnosis of HCC.
研究领域:
生物医学工程
·
分析化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2024
·
IF 4.8
Guiyin Li,Huafu Feng,Xinhao Li,Shengnan Li,Jintao Liang,Zhide Zhou
Glypican-3 (GPC3) is an essential reference target for hepatocellular carcinoma detection, follow-up and prediction. Herein, a dual-signal electrochemical aptasensor based on reduced graphene oxide-cuprous oxide (RGO-Cu 2 O) nanozyme was developed for GPC3 detection. The RGO-Cu 2 O nanoenzyme displayed excellent electron transport effect, large specific surface area and outstanding peroxidase-like ability. The differential pulse voltammetry (DPV) signal of Cu 2 O oxidation fraction and the chronoamperometry ( i-t ) signal of H 2 O 2 decomposition catalyzed by RGO-Cu 2 O nanozyme were used as dual-signal detection. Under optimal conditions, the log-linear response ranges were 0.1 to 500.0 ng/mL with the limit of detection 0.064 ng/mL for DPV technique, and 0.1–50.0 ng/mL for i-t technique (detection limit of 0.0177 ng/mL). The electrochemical aptasensor has remarkably analytical performance with wide response range, low detection limit, excellent repeatability and specificity, good recovery in human serum samples. The two output signals of one sample achieve self-calibration of the results, effectively avoiding the occurrence of possible leakage and misdiagnosis of a single detection signal, suggesting that it will be a promising method in the early biomarker detection.
研究领域:
生物医学工程
·
肿瘤学
·
分析化学
✓ 已验证
DOI
PubMed
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.
研究领域:
癌症诊断
·
生物传感器
·
纳米技术
·
电化学
✓ 已验证
产品关联
DOI
PubMed
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.
研究领域:
生物传感器
·
癌症诊断
·
电化学
·
纳米技术
·
分析化学
✓ 已验证
产品关联
DOI
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.
研究领域:
生物医学工程
·
分析化学
·
纳米技术
·
癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）