INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2017
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IF 3.649
Xiumei Zhu,Altansukh Tsend-Ayush,Zhongyue Yuan,Jing Wen,Jiaxin Cai,Shifu Luo,Jianxu Yao,Junxing Bian,Linfang Yin,Jianping Zhou,Jing Yao
In this study, glycyrrhetinic acid (GA)-modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs) displayed a mean particle size of 133.6 ± 1.2 nm with a low poly-dispersity index (0.224 ± 0.013) and negative zeta potential (−16.30 mV). The drug loading and entrapment efficiency of ETO-TGA PMs were 10.4% and 79.8%, respectively. ETO-TGA PMs also exhibited faster drug release behavior at pH 5.8 and relatively stable drug release at pH 7.4. Confocal laser scanning microscope (CLSM) observations and in vivo imaging studies revealed that TGA PMs displayed higher cellular uptake and selective accumulation at the tumor site, indicating good tumor targetability. Furthermore, ETO-TGA PMs displayed significant cytotoxicity towards HepG2 cells and higher anti-tumor efficacy (75.96%), compared to the control group. This could be due to TGA-mediated targeted drug delivery to the hepatocytes as well as P-gp inhibition. These findings suggest that TGA PMs have the potential to be used as a targeted drug delivery system for hepatic cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
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2018
·Vol. 57
·期 10
·1371-1382
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IF 3.851
Jie Gao,Zhao Wang,Gao-Ju Wang,Na Gao,Jing Li,Yun-Fei Zhang,Jun Zhou,Hong-Xin Zhang,Qiang Wen,Han Jin,Hai-Ling Qiao
Hepatofibrosis is an important susceptibility factor for hepatocarcinogenesis. However, only a handful of cases of hepatofibrosis will develop into hepatocellular carcinoma (HCC). As cytochrome P450 2E1 (CYP2E1) is involved in the metabolism and activation of many known environmental toxicants and procarcinogens, this enzyme may play a role in the development of hepatocarcinogenesis subsequent to hepatofibrosis. Herein, we evaluated whether higher CYP2E1 activity is a risk factor for the development of hepatocarcinogenesis from hepatofibrosis. CYP2E1 activity in fibrotic tissues from 72 HCC patients and in normal liver tissues from 59 control subjects was determined along with the severity of hepatofibrosis in hepatocarcinogenesis patients. Similarly, using a rat diethylnitrosamine-induced hepatocarcinogenesis model, CYP2E1 activity at the hepatofibrosis and hepatocarcinogenesis stages was determined, the correlation between CYP2E1 activity at the hepatofibrosis stage and hepatocarcinogenesis was explored, and the impact of inhibition of CYP2E1 activity on hepatocarcinogenesis was studied. The results showed that while CYP2E1 activity in HCC patients with underlying hepatofibrosis was increased, the severity of hepatofibrosis did not correlate with CYP2E1 activity. In the rat hepatocarcinogenesis model, unexpectedly, CYP2E1 activity was found to decrease from hepatofibrosis to hepatocarcinogenesis. Importantly, however, hepatofibrotic rats with higher CYP2E1 activity developed a more severe form of HCC. Moreover, inhibition of CYP2E1 activity could decrease the occurrence and development of HCC in rats. In conclusion, higher CYP2E1 activity may be a risk factor for hepatocarcinogenesis from hepatofibrosis, which raises the possibility of screening patients with hepatofibrosis for CYP2E1 activity to better estimate their risk for hepatocarcinogenesis.
研究领域:
医学
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药理学
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毒理学
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DOI
PubMed
高影响因子
Scientific Reports
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2017
·Vol. 7
·期 1
·1-10
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IF 4.259
Zhang Zhan,Wang Di,Qiao Shanlei,Wu Xinyue,Cao Shuyuan,Wang Li,Su Xiaojian,Li Lei
Hepatocellular carcinoma (HCC) treatment remains lack of effective chemopreventive agents, therefore it is very attractive and urgent to discover novel anti-HCC drugs. In the present study, the effects of chlorogenic acid (ChA) and caffeic acid (CaA) on HCC induced by diethylnitrosamine (DEN) were evaluated. ChA or CaA could reduce the histopathological changes and liver injury markers, such as alanine transarninase, aspartate aminotransferase, alkaline phosphatase, total bile acid, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The underlying mechanisms were investigated by a data integration strategy based on correlation analyses of metabonomics data and 16 S rRNA gene sequencing data. ChA or CaA could inhibit the increase of Rumincoccaceae UCG-004 and reduction of Lachnospiraceae incertae sedis , and Prevotella 9 in HCC rats. The principal component analysis and partial least squares discriminant analysis were applied to reveal the metabolic differences among these groups. 28 different metabolites showed a trend to return to normal in both CaA and ChA treatment. Among them, Bilirubin, L-Tyrosine, L-Methionine and Ethanolamine were correlated increased Rumincoccaceae UCG-004 and decreased of Lachnospiraceae incertae sedis and Prevotella 9 . These correlations could be identified as metabolic and microbial signatures of HCC onset and potential therapeutic targets.
研究领域:
医学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Oncotarget
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2017
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IF 5.168
Hai-Ning Liu,Hao Wu,Yan-Jie Chen,Yu-Jen Tseng,Enkhnaran Bilegsaikhan,Ling Dong,Xi-Zhong Shen,Tao-Tao Liu
Background Many new diagnostic biomarkers have been developed for hepatocellular carcinoma (HCC). We selected two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and attempted to establish appropriate models. Methods We reviewed the diagnostic efficiencies of all microRNAs identified by previous diagnostic tests. Then we chose appropriate microRNAs to validate the diagnostic efficiencies, and determined the optimal combination. We included 66 patients with HCC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was performed, and we used three multivariate statistical methods to establish diagnostic models. The concentration of alpha feto-protein (AFP) was determined for comparison with the novel models. Results 82 published studies and 92 microRNAs were ultimately included in this systematic review. Seven microRNAs were selected for further validation of their diagnostic efficiencies. Among which, miR-21, miR-106b, miR-125b, miR-182 and miR-224 had a significantly different expression in HCC patients. The combination of miR-21, miR-106b and miR-224 had the highest area under the curve (AUC) at 0.950 with a sensitivity of 80.3% and a specificity of 92.7%. The GC/MS analysis exhibited an excellent diagnostic value and the AUC reached 1.0. In comparison, the AUC of the traditional biomarker, AFP, was 0.755. Conclusion MicroRNAs and metabolomics shows promising potential as new diagnostic methods due to their high diagnostic value compared with traditional biomarkers.
研究领域:
肿瘤学
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分子生物学
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代谢组学
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DOI
PubMed
高影响因子
Biology Direct
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2025
·Vol. 20
·期 1
·1-15
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IF 4.9
Wei Xiaoyong,Zou Long,Huang Yanqing,Qiu Chuan,Cheng Guang,Chen Ye,Rao Jun
Background Hepatocellular carcinoma (HCC) is among the deadliest cancers globally. Yes-Associated Protein (YAP), a Hippo pathway effector, crucially regulates cell proliferation and apoptosis. Recent research has implicated YAP’s role in HCC progression, but the mechanisms are unclear. This study aims to clarify YAP’s function in HCC, emphasizing its regulation of key pathways and targets. Results Gene knockout and overexpression models were established in nude mice and cell lines of HCC cells to investigate YAP’s impact on tumorigenesis. Additionally, functional assays and molecular biology techniques were employed to identify YAP’s regulatory networks. The study demonstrates that LDHA-regulated lactate production promotes YAP activation and malignant phenotypes in HCC. Overexpression of LDHA in HepG2 and Huh7 cells increased lactate levels and activated the YAP pathway, enhancing cell proliferation, migration, and invasion. Lactate treatment also promoted these malignant phenotypes by inhibiting YAP phosphorylation at Ser127. In a xenograft model, lactate accelerated tumor growth through YAP activation. YAP lactylation at K102 antagonized its Ser127 phosphorylation, further promoting malignant progression. Conclusions This study highlights the significance of YAP in HCC pathogenesis, providing insights into potential therapeutic targets for HCC management. Graphical
研究领域:
肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Bokai Zhou,Jie Feng,Yi Zhang,Ting Zhang,Caiwei Hu,Shuyan Liu,Xu Yin,Mingshi Jin,Yu Bai
Efficient purifying and analyzing exosomes remain challenging in noninvasive liquid biopsy diagnostics. Nanomaterials-assisted laser desorption/ionization mass spectrometry (LDI-MS) provides a powerful approach for screening exosome metabolites. Herein, we developed a novel bifunctional bowl-shaped organosilica-based nanoplatform, the streptavidin-functionalized Pt-deposited mesoporous organosilica nanobowl (SA@Pt-MONB), as an exosome capture vessel and inherent LDI-MS matrix for sequential exosome capture and metabolite analysis. We established a simple, rapid, efficient, and cost-effective serum exosome diagnostic platform with low sample consumption. The unique bowl-shaped morphology provides excellent exosome capture efficiency through more interaction sites (with a maximum value of 97.53 %) and improves light trapping for downstream LDI-MS. The aromatic ring in the framework and deposited Pt NPs facilitate hot carrier production and charge transfer, improving the ionization efficiency of metabolites in LDI-MS analysis. As the inherent matrix, SA@Pt-MONB synergistically enhanced the high-throughput LDI-MS analysis of exosome metabolites. Machine learning algorithms were applied to effectively distinguish hepatocellular carcinoma (HCC) from healthy donors (HD) using serum exosome metabolic profile. A metabolite biomarker panel comprising four key metabolites was proposed for the diagnosis of HCC with AUC value from 0.985 to 0.987. This work demonstrates the significant potential of efficient exosome purification and metabolite analysis based on nanomaterials, promising in noninvasive liquid biopsy of diseases diagnosis and precision medicine.
研究领域:
医学诊断
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生物化学
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纳米技术
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DOI
高影响因子
MATERIALS CHEMISTRY AND PHYSICS
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2025
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IF 4.7
Xue-Jie Zhao,Lin-Song Li,Peng-Wei Chen,Dong Cheng,Bang-Bang Liu,Mei-Xia Zhao
So far, the single treatment has failed to achieve the desired outcomes in cancer treatment, significantly contributing to the surge in interest in multimodal synergistic therapies for cancer. In this study, we developed a multifunctional biomimetic nanoplatform (GNS@PDA-Pt-DOX-9R-P201, GPPtD9R NPs), which consists of photothermal reagents gold nanostar (GNS), biomimetic material polydopamine coating (PDA), targeting peptide (9R-P201) and two kinds of chemotherapeutic agent doxorubicin (DOX) and cis-platinum (CDDP). The particle size of the GPPtD9R NPs was 255 ± 10.56 nm, the zeta potential was 3.75 ± 0.13 mV, the photothermal conversion efficiency was 21.33%, and the loading rates of DOX and CDDP were 5.98%% and 7.67%, respectively. Under 808 nm light irradiation, the GPPtD9R NPs elevated the temperature beyond the safe threshold for cells. The modification with 9R-P201 enabled targeted delivery, and upon laser irradiation, the GPPtD9R NPs released DOX and CDDP in the tumor, achieving the synergistic treatment of hepatocellular carcinoma (HCC) through photothermal therapy (PTT) and dual chemotherapy, which not only enhances the anti-tumor effect but also minimizes systemic toxicity. The platform achieved a remarkable 90.3% tumor suppression rate for HCC, and no abnormalities in biochemical blood indicators or damage to normal tissues were found at the end of the treatment. Overall, GPPtD9R NPs exhibit potent anti-HCC efficacy and exceptional biocompatibility, presenting a novel strategy for tumor therapy.
研究领域:
肿瘤学
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纳米医学
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生物材料科学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Guangchao Xie,Bingjie Li,Shuyue Guo,Wenjing Hou,Yao Wang,Jiamei Liu,Jialin Zhu,Luchen Chang,Xiaoqing Wang,Xiaoyi Wang,Jinbin Pan,Xi Wei
Percutaneous local thermal therapy, containing radio frequency and microwave ablation, is widely utilized in the clinical management of hepatocellular carcinoma (HCC) due to its minimal invasiveness and favorable therapeutic outcomes. However, its further development is limited by a prolonged ablation duration and the risk of excessive heating. Magnetic hyperthermia therapy (MHT) provides a new perspective for percutaneous tumor thermal ablation due to its superior tissue penetration capability and safety. Herein, an iron foam–agarose gel–drug (IF-Aga-drug) implant is prepared using a minimalistic method for percutaneous combination therapy of HCC. The excellent conductivity of IF endows it with strong heating capability owing to eddy current loss in an alternating magnetic field (AMF), while the abundant pores provide ample space for drug loading. Agarose gel imparts the IF platform with universal and efficient drug-loading capacity and controlled drug-release capability that is responsive to magnetic hyperthermia. Doxorubicin (DOX) is utilized as a representative drug to construct the IF-Aga-DOX implant, which is successfully employed in ultrasound-guided, magnetic hyperthermia-based combination chemotherapy for orthotopic HCC in rabbits under ultralow-power magnetic field intensities (Happl·fappl = 2.25 × 108 A m–1 s–1). The developed IF-Aga-drug implant platform offers a convenient and versatile strategy for percutaneous tumor therapy.
研究领域:
医学工程
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肿瘤学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
BMC Pharmacology & Toxicology
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2021
·Vol. 22
·期 1
·1-11
·
IF 2.483
Li Danni,Liu Shaogang,Zhu Jiahao,Shen Liqun,Zhang Qi ying,Zhu Hua
Background The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have anticancer properties, but doses at therapeutic levels have unacceptable side effects. Here we investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug. Methods Synthesized TPGS-FA was characterized by FTIR, UV-visible and 1 H NMR spectroscopy, and TPGS loaded with NC was evaluated for its ability to induce apoptosis in Huh7 cells by Annexin V/PI and MTT assays, and observed by laser scanning confocal microscopy and inverted phase contrast microscopy. Results TPGS-FA/NC complexes were prepared successfully, and were homogenious with a uniform size of ~ 14 nm diameter. NC was released from the TPGS-FA/NC complexes in a controlled and sustained manner under physiological conditions (pH 7.4). Furthermore, its cytotoxicity to hepatocarcinoma cells was greater than that of free NC. Conclusions TPGS-FA is shown to be useful carrier for drugs such as NC, and TPGS-FA/NC could potentially be a potent and safe drug for the treatment of hepatocellular carcinoma.
研究领域:
药学
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肿瘤学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Chaochao Wen,Rina Cheng,Tao Gong,Yu Huang,Dan Li,Xuhua Zhao,Baofeng Yu,Dan Su,Zhiling Song,Wenting Liang
Synergistic photochemical therapy with high performance and weak side effects is of great importance in hepatocellular carcinoma (HCC) treatment, therefore ingenious construct of nano-based therapy agents with accurate drug delivery and high photothermal conversion efficiency is of critical to the cancer therapy. Herein, an organic-inorganic hybrid nanomaterial (MGO@CD-CA-HA) has been constructed successfully by coating the β-cyclodextrin-cholic acid-hyaluronic acid polymer (CD-CA-HA) onto the Fe 3 O 4 -graphene oxide (MGO). The MGO@CD-CA-HA revealed satisfactory multiple-targeted features including the cholic acid supplied hepatic-target, CD44-receptor target of hyaluronic acid and magnetic target of Fe 3 O 4 . Meanwhile, the hydrophobic antitumor drug camptothecin (CPT) was easily loaded by MGO@CD-CA-HA to form the MGO@CD-CA-HA/CPT nanocomposite, and the maximum theoretical adsorption capacity can reach 847.4 mg/g. Based on the facile photothermal response of MGO , the near-infrared radiation (808 nm) induced local hyperthermia was directly generated the apoptosis of tumor cells while triggered the release of CPT. Comparing with other kinds of cancer cells and normal hepatocyte cells, this PCT system provides a significant inhibitory effect for the liver cancer cells in vitro . Furthermore, the synergistic photochemical therapy presented the strong antitumor effect (the tumor inhibition rate > 90 %) in vivo . Thus, this study provided a promising multiple-targeted nanocarrier for chemo-photothermal combination therapy of liver cancer.
研究领域:
医学
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生物材料学
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肿瘤学
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产品关联
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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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2024
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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
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肿瘤学
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分析化学
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产品关联
DOI
高影响因子
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