JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-18
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IF 9.429
Chen Xuehua,Huang Yongquan,Chen Hui,Chen Ziman,Chen Jiaxin,Wang Hao,Li Dan,Su Zhongzhen
Background Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. Results Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. Conclusions This work provides a new paradigm for the treatment of residual HCC after IRFA. Graphical Abstract
研究领域:
肿瘤学
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纳米技术
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药理学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2024
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IF 5.7
Wenjie Zhu,Hong Qian,Shengya Cao,Wei Xia,Xilong Wang,Jing Jin,Xin Wang,Hao Zhang,Dongsheng Liu,Ying Chen
Background The early detection of Hepatocellular Carcinoma (HCC) is crucial for improving patient survival rates.Early diagnosis of HCC can significantly enhance treatment outcomes and reduce disease progression. Antigen detection of tumor markers is one of the important diagnostic methods for HCC. However, Traditional antigen detection methods often rely on heavy detection equipment, involve lengthy turnaround times, and must be conducted in laboratory settings. Therefore, there is a clear need for a portable, low-skill, rapid sample-to-result detection method for early HCC biomarkers. Results We propose a new platform based on electrowetting-on-dielectric digital microfluidic(EWOD-DMF) for the detection of early-stage HCC biomarkers, enabling the quantitative measurement of Alpha-Fetoprotein (AFP), the proportion of AFP-L3 in total AFP (AFP-L3%), and Des-Gamma-Carboxy Prothrombin (DCP). First, serum samples are processed through the microfluidic system, achieving the separation of AFP-L3 within 10 min. Next, immunoassays are performed within 15 min, using magnetic particles to capture biomarkers such as AFP, AFP-L3, and DCP, followed by enzymatic reactions that generate detectable signals. Each chip can simultaneously detect three biomarkers from five different samples, allowing for a total of fifteen targets to be tested, with only approximately 2.4 μL of serum required for each biomarker detection. Ultimately, data are analyzed with dedicated software to quantitatively measure the HCC biomarkers. The detection limits for AFP or AFP-L3 and for DCP are 0.24 ng/mL and 1.89 ng/mL, respectively. Significance This study presents a EWOD-DMF platform for early-stage HCC diagnosis, capable of simultaneously detecting multiple samples and biomarkers, thus improving detection efficiency and diagnostic accuracy. Moreover, the platform has POCT capability, with advantages in portability and cost-effectiveness, providing clinicians and primary healthcare institutions with a fast and convenient solution for early-stage HCC diagnosis.
研究领域:
医学工程
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肿瘤学
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DOI
PubMed
高影响因子
PROTEIN EXPRESSION AND PURIFICATION
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2022
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IF 2.025
Zhiting Lao,Shuanqi Li,Jinhui Liang,Jingyi Su,Xin Gong,Xiping Cui,Suqing Zhao
Glypican-3 (GPC3) has a promise to be the diagnostic biomarker as well as therapeutic target for hepatocellular carcinoma (HCC). Nanobody have the great potential in clinical diagnosis and treatment for their characteristics of small size, high solubility, stability, manipulability, binding advantages, and ease of production. In this study, the recombinant glypican-3-N terminal (GPC3-N) protein was expressed as inclusion body in E. coli BL21(DE3)pLysS cells and then purified, which is then used as the immunogen to construct nanobody phage library. The positive clone (named MF15) was obtained by four rounds of bio-panning, and then transformed into the E. coil TOP10F’ cells to express nanobody protein, with the molecular weight of 19 kDa. Both Western blot and immunofluorescence analysis revealed that bacterially expressed GPC3-N protein is biologically active, and MF15 could specifically recognized native GPC3 expressed in HepG2 cells. The results in this study would provide the technical support for the development of diagnostic kits and antibody drugs targeting GPC3.
研究领域:
分子生物学
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癌症研究
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生物技术
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2025
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IF 7.7
Wenwei Wu,Lixia Qian,Jie Shen,Hongmei Li,Liang-cheng Li
Cancer remains a leading cause of mortality worldwide, with China bearing a particularly high burden. Early detection through reliable biomarkers is essential for improving patient outcomes. This study reports the development and validation of a highly specific aptamer-based biosensor for detecting the complement protein C1QC, a promising cancer biomarker. Using a multi-step selection process involving Magnetic beads-SELEX, qPCR, flow cytometry, high-throughput sequencing, surface plasmon resonance (SPR), pull-down, and western blotting, we identified Apt 13, a slow-dissociation aptamer with high specificity and affinity for C1QC (K D = 48.7 nM). SPR confirmed the formation of a sandwich complex between Apt 13, C1QC, and Anti_C1QC, confirming their distinct binding sites. We developed two biosensor platforms based on this aptamer: the enzyme-linked antibody-aptamer sandwich (ELAAS) and chemiluminescent antibody-aptamer sandwich (CLAAS) biosensors. The ELAAS biosensor, designed for visual colorimetric detection, demonstrated a limit of detection (LOD) of 98 ng/mL. In contrast, the CLAAS system, utilizing acridinium ester-modified antibodies, achieved an enhanced LOD of 0.375 ng/mL. Receiver Operating Characteristic (ROC) analysis on serum samples from 75 hepatocellular carcinoma (HCC) patients and 20 healthy controls yielded an AUC of 0.942, with 86.67 % sensitivity and 95.00 % specificity, demonstrating CLAAS’s high diagnostic accuracy in differentiating HCC from controls. Further testing in HCC patient serum samples revealed significantly elevated C1QC levels compared to healthy controls, underscoring C1QC’s potential as a HCC cancer biomarker. Apt 13 presents a promising tool for the development of innovative, sensitive, and cost-effective diagnostic technologies for C1QC detection and may offer future potential for targeted therapies.
研究领域:
癌症研究
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分子诊断
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生物传感器
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适配体技术
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蛋白质组学
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临床诊断
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产品关联
DOI
高影响因子
TALANTA
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2024
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IF 5.6
Lvhong Gong,Shengxi Wu,Junjie Liu,Mingjun Zhang,Jinghao Zhuang,Doudou Xu
An ultrasensitive immunosensor of Cys/Au@TiO 2 based on disposable screen-printed electrodes (SPE) for PIVKA-II detection for hepatocellular carcinoma (HCC) diagnosis was developed by utilizing Cystine (Cys) and nanocomposite Au@TiO 2 . Firstly, HAuCl 4 underwent a reduction reaction with NaBH 4 , then Au nanoparticles were coated onto TiO 2 nanoparticles. Followed, Cys/Au@TiO 2 was formed through self-assembly of cysteine to allow the monoclonal antibody of abnormal thrombospondin to bound to the amino group on the surface of the composite by covalent bonding. The mechanism is to determine the changes in the current of the sensor caused by the specific binding of the abnormal prothrombin monoclonal antibody adsorbed by the complex with its antigen. The Cys/Au@TiO 2 immunosensor was fully characterized by various analytical approaches and it showed a wide linear testing range of 1–10000 pg mL −1 (R 2 = 0.991) and the limit of detection down to 0.77 pg ml −1 , with highly sensitivity and specificity. The results showed that the developed immunosensor platform can effectively detect trace amounts of PIVKA-II protein and has potent clinical application for HCC diagnosis.
研究领域:
生物医学工程
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分析化学
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癌症诊断
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
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2019
·Vol. 186
·期 6
·1-8
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IF 5.479
Li Yufei,Zhang Huanhuan,Cai Xuan,Zhao Hongli,Magdassi Shlomo,Lan Minbo
Two kinds of carbon-based nanozymes were constructed from the same precursor of zeolitic imidazolate framework-8 (ZIF-8) for O 2 •− determination. Hollow carbon cubic nanomaterial (labelled as HCC) was obtained by chemically etching ZIF-8 with tannic acid and a subsequent calcination. A porous carbon cubic nanomaterial (labelled as PCC) was prepared by directly pyrolysis. Then HCC and PCC were immobilized on the surface of screen printed carbon electrodes (SPCE), fabricating HCC and PCC modified electrodes (denoted as HCC/SPCE and PCC/SPCE). HCC/SPCE, best operated at −0.5 V (vs. Ag/AgCl), has a sensitivity of 6.55 × 10 2 nA μM −1 cm −2 with a detection limit of 207 nM (at S/ N = 3) for O 2 •− sensing. And PCC/SPCE, best operated at −0.4 V (vs. Ag/AgCl), exhibited a superior performance for O 2 •− detection with a sensitivity of 1.14 × 10 3 nA μM −1 cm −2 and a low detection limit of 140 nM (at S/ N = 3). The two sensors possess excellent reproducibility and stability. They were used to sense O 2 •− released from HeLa cells.
Illustration of the synthesis of the hollow carbon cubic nanomaterial (HCC) and of the porous carbon cubic nanomaterial (PCC), and the scheme for detection of superoxide anions in HeLa cell.
研究领域:
材料科学
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生物化学
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分析化学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
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2019
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IF 3.046
Xie Weng,Lixian Zeng,Feifei Yan,Mengxue He,Xiuqiong Wu,Dayong Zheng
Purpose: The sensitivity of advanced hepatocellular carcinoma (HCC) to Sorafenib is low. The purpose of this study was to investigate the effects of cyclin-dependent kinase inhibitor 2B (CDKN2B) gene on the prognosis of HCC and the sensitivity of HCC cells to Sorafenib. Patients and methods: Streptavidin-perosidase (SP) staining was performed to determine the expression of CDKN2B in HCC tissues and adjacent tissues. The cell counting kit-8 (CCK-8) assay was carried out to determine cell viability. CDKN2B mRNA and protein were tested by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. CDKN2B gene was silenced or over-expressed in the cells by plasmid transfection technique. Flow cytometry was carried out to detect cell cycle and apoptosis. Results: SP staining results showed that CDKN2B was positive in adjacent tissues and in HCC tissues from partial response (PR) patients, CDKN2B was slightly positive in stable disease (SD) patients, but negative in progression disease (PD) patients. The survival rate of patients with low expression of CDKN2B was low. Up-regulation of CDKN2B expression could promote the pro-apoptotic effect of Sorafenib and cell arrest in G1 phase. When the CDKN2B gene expression was down-regulated, the cell apoptosis rate and the proportion of cells treated with Sorafenib in G1 phase decreased. Silencing CDKN2B reversed CDKN2B overexpression caused by Sorafenib. Conclusion: CDKN2B genes were lowly expressed in tumor tissues from HCC patients who were treated with Sorafenib and had a poor prognosis. Up-regulation of CDKN2B promoted sensitivity of HCC to Sorafenib, and similarly down-regulation of CDKN2B reduced the sensitivity.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2026
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IF 6.4
Gaoxuan Shao,Chenceng Sun,Chenhao Ye,Ying Liu,Jiashu Pan,Yujing Liu,Lu Lu,Lei Wang,Zemin Lin,Fan Yang,Guang Ji,Hanchen Xu
Luteolin significantly reduces tumor burden and fibrosis in a MASH-HCC mouse model. • Luteolin attenuates hepatic lipid accumulation by inhibiting de novo lipogenesis. • The protective effects of luteolin are mediated via the AMPK/ACC signaling pathway. • Inhibition of AMPK abolishes the lipid-lowering benefits of luteolin in hepatocytes. Aims Metabolic dysfunction-associated steatohepatitis (MASH) is a primary driver of hepatocellular carcinoma (HCC), yet effective therapeutic interventions remain limited. While luteolin is known for its anti-inflammatory properties, its efficacy and underlying mechanism in the MASH-HCC transition are not fully understood. This study investigated the protective effects of luteolin against MASH-HCC and the role of the AMPK/ACC signaling pathway in this process. Materials and methods In vivo , a MASH-HCC mouse model was established using diethylnitrosamine (DEN) combined with a high-fat, high-cholesterol (HFHC) diet. Mice were treated with vehicle or luteolin (50 or 100 mg/kg) for 26 weeks. Progression was monitored via serum alpha-fetoprotein (AFP), histological analysis, and Western blotting. In vitro , HepG2 and Huh-7 cells were challenged with cholesterol and treated with luteolin. The AMPK inhibitor BAY-3827 was employed to verify whether the metabolic benefits of luteolin were pathway-dependent. Key findings Luteolin treatment significantly reduced tumor burden, lowered serum AFP levels, and attenuated hepatic lipid accumulation and fibrosis in MASH-HCC mice. In vitro results mirrored these findings, showing that luteolin reduced cholesterol-induced lipid loading. Mechanistically, luteolin increased the phosphorylation of AMPK and its downstream target, ACC. Furthermore, pharmacological inhibition of AMPK with BAY-3827 abolished the lipid-lowering effects of luteolin in hepatic cells, confirming that its therapeutic benefits are mediated through AMPK activation. Significance Luteolin suppresses the progression of MASH to HCC by activating the AMPK/ACC signaling pathway and subsequently inhibiting de novo lipogenesis. These findings highlight luteolin as a promising potential therapeutic candidate for the prevention and treatment of MASH-related liver cancer. Download: Download high-res image (314KB) Download: Download full-size image
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DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2024
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IF 3.3
Yao Deng,Yujie Li,Mingyue Yang,Yang Gao,Xuling Luo,Hanbin Chen,Meng Guo,Xuefeng Yang,Yongzhang Liu,Jun He,Bin Lu,Naxin Liu
Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Nano Convergence
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2024
·Vol. 11
·期 1
·1-15
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IF 13.4
Chen Yichi,Li Xudong,Shang Haitao,Sun Yucao,Wang Chunyue,Wang Xiaodong,Tian Huimin,Yang Huajing,Zhang Lei,Deng Liwen,Yang Kuikun,Wu Bolin,Cheng Wen
The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy.
研究领域:
肿瘤学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
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2024
·
IF 1.6
Xixuan Gu,Qingning Li,Xiaohui Song,Chen Chen,Xiaobing Yin,Jiayu Shen,Rui Yu,Keqi Tang
The concentration of alpha-fetoprotein (AFP) generally increases in the serum of hepatocellular carcinoma (HCC) patients. Hence, AFP is a biomarker for HCC detection, diagnosis, and treatment. However, the sensitivity is unsatisfactory. Here a fluorescent probe based on CdTe quantum dots (QDs-AFPAb) was prepared and a simple sensitive fluorescence immunoassay on nitrocellulose membranes (NFIA) was developed for alpha-fetoprotein. This method exhibited a low detection limit of 2.18 pg/mL with a linear range from 10 to 1.0 × 107 pg/mL. In addition, the sensitivity allowed the identification of HCC and non-HCC serum. This method is sensitive, easy, and low-cost for the diagnosis of HCC.
研究领域:
生物技术
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分析化学
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医学诊断
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癌症研究
✓ 已验证
产品关联
DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2021
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IF 3.503
Chun Li,Xin-You Pan,Mingyun Ma,Jun Zhao,Fengda Zhao,Ya-Ping Lv
Context Astragalus polysaccharin (APS), an extract of Astragalus propinquus Schischk, exerts antitumor effects in hepatocellular carcinoma (HCC).Objective This study investigated the mechanism of action of APS in HCC.Materials and methods Tumour-associated macrophages (TAMs) were treated with APS (0, 8, 16 mg/mL) for 24 h. APS (16 mg/mL)-treated TAMs were co-cultured with MHCC97H/Huh7 cells for 24 h. Finally, BALB/c nude mice were divided into PBS, APS (50 mg/kg), APS (100 mg/kg), APS (200 mg/kg) groups: mice were inoculated with Huh7 cells to construct tumour xenograft model, followed by administration of APS (50, 100, 200 mg/kg) or PBS daily for 30 days. Cell proliferation, migration, invasion, tumour growth, macrophage markers and proportions were measured.Results APS 16 mg/mL treatment enhanced the expression of M1 macrophage markers (iNOS, IL-1β and TNF-α) and M1 macrophage proportions, while reducing the expression of M2 macrophage markers (IL-10, Arg-1) and M2 macrophage proportions in TAMs. Moreover, the APS-mediated M1 phenotype of TAMs significantly repressed cell proliferation, migration and invasion of MHCC97H and Huh7 cells. Moreover, APS (50, 100, 200 mg/kg) enhanced M1 macrophage proportions and reduced M2 macrophage proportions in the tumour tissues, and thus inhibited tumour growth of HCC.Discussion and conclusions APS inhibits HCC-like phenotypes in a murine HCC model through repression of M2 polarization of TAMs. This work provides a novel theoretical basis for the application of APS in the clinical treatment of HCC.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
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