Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 43
·6822-6827
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IF 5.047
Fanpeng Kong,Ying Li,Chao Yang,Xiao Li,Junlin Wu,Xiaojun Liu,Xiaonan Gao,Kehua Xu,Bo Tang
Identifying cancer at the cellular level during an early stage offers the hope of greatly improved outcomes for cancer patients. As potential cancer biomarkers, nitroreductase (NTR) and human quinine oxidoreductase 1 (hNQO1) are overexpressed in many type of cancer cells. Simultaneous detection of these two biomarkers would benefit diagnostic precision in related cancers without yielding false positive results. Herein, based on a dye generated in situ strategy, a dual-enzyme-responsive probe, CNN, was rationally designed and synthesized by installing p-nitrobenzene and trimethyl-locked quinone propionic acid groups, which are specific for NTR and hNQO1, respectively, into a single fluorophore. This probe is only activated in the presence of both NTR and hNQO1 and produces a large fluorescence response, enabling the detection of both endogenous NTR and hNQO1 activity in living cells. The imaging results indicate that the CNN probe differentiates cancer cells (HeLa, MDA-MB-231 and HepG2 cells) from normal liver HL-7702 cells owing to the existence of relatively high endogenous levels of both biomarkers in these cancer cells.
研究领域:
癌症生物学
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生物化学
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分子生物学
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细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2014
·
IF 0
Meihao Liang,Xiaoliang Zheng,Linglan Tu,Zhen Ma,Zunyuan Wang,Dongmei Yan,Zhengrong Shen
In order to study the liver targeting of the N-galactosylated chitosan (GC) polymer in liver, we first conjugated the lactobionic acid with chitosan (CS) to obtain the carrier of GC with different degree of substitution of lactosyl group. Western blot was performed to detect the expression levels of the asialoglycoprotein receptors (ASGPR) in the cell lines of HepG2, SMMC-7721, and HL-7702. The protein level of ASGPR was lower in HepG2 compared to HL-7702 and SMMC-7721. Although all treated by CS, viabilities of HL-7702 and HepG2 did not experience any significant drop, while viability of SMMC-7721 decreased 15% on average from control. It was the first data about the inhibitory effect of GC on the liver cells. Fluorescein isothiocyanate (FITC) labeled GC (GC-FITC) was injected intravenously into mice at a dose of 0.02 μmol/mouse. GC-FITC showed maximum liver localization at 5 min and even detectable at 48 h after injection. Further, the accumulation of GC in liver was about 5.4-fold higher than that of CS. In conclusion, GC demonstrated its higher efficacy in drug liver targeting and thus could be a more promising drug or gene carrier in future therapies.
研究领域:
药理学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Shuyun Wu,Na Li,Chuan Yang,Li Yan,Xuan Liang,Meng Ren,Liqun Yang
The cationic branched tea polysaccharide (CTPSA) derivative bearing N -acylurea and 3-(dimethylamino)-1-propylamine residues was synthesized and characterized using FTIR and 1 H NMR spectroscopy. A nonspecific siRNA (NsiRNA) was used as a model molecule of functional siRNA that could downregulate over-expressed glycometabolism enzymes in the liver. The result from the agarose gel electrophoresis confirmed that the CTPSA and NsiRNA could form stable complexes when their weight ratio was larger than 18. The zeta potentials and sizes of the complexes were in the range of +8–+15 mv and 120–150 nm, respectively. The CTPSA/NsiRNA complex was observed as nanoparticles with a spherical shape of approximately 100 nm using scanning electron microscopy. The CTPSA derivative and the CTPSA/NsiRNA complexes exhibited lower cytotoxicity in HL-7702 cells when compared with the branched PEI (bPEI) and bPEI/NsiRNA complexes assessed by the Cell Counting Kit-8 assay. The results of flow cytometric analysis and laser confocal microscopy indicated that the CTPSA derivative could effectively target the transfer of the NsiRNA to HL-7702 cells. This work provides a potential approach to promote the CTPSA derivative as a nonviral vector for targeted delivery of functional siRNA to hepatocytes.
研究领域:
药理学
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分子生物学
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生物技术
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基因治疗
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产品关联
DOI
PubMed
高影响因子
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
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2024
·
IF 3.2
Jia Shi,Yuhua Liu,Shuxiang Jiao,Tao Wu,Ai Wang,Wenming Wang,Leilei Xie,Yanhong Liu,Hongfei Wang
Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] ( 1 – 4 ) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, l -valine) and characterized by 1 H NMR, 13 C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes 1 – 4 inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes.
研究领域:
无机化学
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生物化学
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药学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Donghan Bai,Zihao Zhang,Jingyue Gao,Qiaochu Wang,Remy Macdonald,Ziwen Xu,Shumin Chen,Nanxi Huang,Lu Luo
Background: Leukemia is a malignant hematologic disease that poses a serious threat to human health. Realgar-Indigo Naturalis formula (RIF), a traditional Chinese medicine formula, have demonstrated anti-tumor activity, but its mechanisms of action remain unclear.Objective: This study aimed to establish a zebrafish HL-60 tumor transplantation model to investigate the anti-leukemic effects of RIF and explore its underlying mechanisms.Methods: The zebrafish HL-60 tumor transplantation model was established, with RIF as the intervention drug and all-trans retinoic acid (ATRA) as the control. Anti-tumor efficacy was assessed via pharmacodynamic analysis. Transcriptomic analysis further elucidated gene expression profiles, differentially expressed genes, and relevant biological pathways.Results: RIF significantly reduced tumor cell fluorescence intensity, demonstrating anti-tumor efficacy. Additionally, it improved HL-60-induced liver damage in zebrafish, as evidenced by a reduction in fatty vacuolar degeneration in liver tissue. Transcriptomic analysis revealed that ATRA mainly affected the FoxO signaling pathway, PI3K-Akt signaling pathway, apoptosis, and complement and coagulation cascades in leukemia treatment. RIF primarily influenced the ubiquitin-proteasome system, ferroptosis, and glutathione metabolism. The combination of ATRA and RIF also affected autophagosome and lysosome pathways, in addition to the aforementioned pathways.Conclusion: RIF exhibit significant anti-tumor effects through modulation of multiple pathways. This study provides a theoretical foundation for the potential clinical application of RIF in leukemia treatment.
研究领域:
肿瘤学
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药理学
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中医学
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发育生物学
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毒理学
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基因组学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xiaowei Niu,Jing Zhang,Jingjing Zhang,Lu Bai,Shuwen Hu,Zheng Zhang,Ming Bai
Myocardial ischemia/reperfusion (MI/R) injury, a major contributor to poor prognosis in patients with acute myocardial infarction, currently lacks effective therapeutic strategies in clinical practice. The long noncoding RNA (lncRNA) Oip5-as1 can regulate various cellular processes, such as cell proliferation, differentiation, and survival. Oip5-as1 may have potential as a therapeutic target for MI/R injury as its upregulated expression has been associated with reduced infarct size and improved cardiac function in animal models, although how to effectively and safely overexpress Oip5-as1 in vivo remains unclear. Lipid nanoparticles (LNPs) are a versatile technology for targeted drug delivery in numerous therapeutic applications. Herein, we aimed to assess the therapeutic efficacy and safety of LNPs coloaded with Oip5-as1 and a cardiomyocyte-specific binding peptide (LNP@Oip5-as1@CMP) in a murine model of MI/R injury. To achieve this, LNP@Oip5-as1@CMP was synthesized via ethanol injection method. The structural components of LNP@Oip5-as1@CMP were physicochemically analyzed. A hypoxia/reoxygenation (H/R) model in HL-1 cells and coronary artery ligation in mice were used to simulate MI/R injury. Our results demonstrated that LNPs designed for cardiomyocyte targeting and efficient Oip5-as1 delivery were successfully synthesized. In HL-1 cells, LNP@Oip5-as1@CMP treatment significantly reduced mitochondrial apoptosis caused by H/R injury. In the murine MI/R model, the intravenous administration of LNP@Oip5-as1@CMP significantly decreased myocardial infarct size and improved cardiac function. Mechanistic investigations revealed that Oip5-as1 delivery inhibited the p53 signaling pathway. However, the cardioprotective effects of Oip5-as1 were abrogated by administrating Nutlin-3a, a p53 activator. Furthermore, no signs of major organ damage were detected after LNP@Oip5-as1@CMP injection. Our study reveals the therapeutic potential of LNPs for targeted Oip5-as1 delivery in mitigating MI/R injury. These findings pave the way for advanced targeted treatments in cardiovascular diseases, emphasizing the promise of lncRNA-based therapies.
研究领域:
心血管疾病
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纳米技术
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2017
·Vol. 184
·期 1
·60-74
·
IF 2.399
Tao Ran,Wang Chengzhang,Zhang Changwei,Li WenJun,Zhou Hao,Chen Hongxia,Ye Jianzhong
The structure and bioactivity of Ginkgo biloba leaves polyprenol (GBP) are similar to that of dolichol which widely exists in human and mammalian organs. GBP possesses potential pharmacological activities against cancer. This study involved oil-in-water type nanoemulsion (NE) loading GBP was prepared by dissolving polyprenol in nanoemulsion of sodium tripolyphosphate (TPP)/TiO 2 solution, Triton X-100, and 1-octanol by inversed-phase emulsification (EIP) and ultrasonic emulsification (UE) method. Folic acid (FA)-coupled chitosan (CS) nanoparticles (NPs), GBP-FA-CS-NPs and GBP-TiO 2 -FA-CS-NPs, were fabricated by ionic cross-linking of positively charged FA-CS conjugates and negatively charged nanoemulsion with TPP/TiO 2 . And characterizations of them were investigated by TEM, SEM, FTIR, particle size, and zeta potential. The cytotoxic and genotoxic effects of GBP-TiO 2 -FA-CS-NP treatment were higher than GBP-NE, GBP-FA-CS-NPs, TiO 2 -NE, GBP-TiO 2 -NE, TiO 2 -FA-CS-NPs, and GBP-TiO 2 -FA-CS-NP treatment at the same tested concentrations in HepG2 cells. GBP-TiO 2 -FA-CS-NPs at low TiO 2 concentration (from 1 to 2.5 μg/ml) showed good inhibition capacity on HepG2 cells and low cytotoxic and genotoxic effects on HL-7702 cells. The possible mechanism of cytotoxicity on GBP-TiO 2 -FA-CS-NPs against HepG2 cells is by preventing excessive intracellular Ca 2+ into extracellular spaces via inhibiting Ca 2+ -ATPase and Ca 2+ /Mg 2+ -ATPase.
研究领域:
药理学
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纳米技术
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毒理学
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癌症研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Linhao Xu,Daqiang He,Yirong Wu,Lishui Shen,Yongmei Wang,Yizhou Xu
Background Heart failure (HF) is a common cardiovascular syndrome. Tanshinone IIA (Tan IIA) is a pharmacologically active monomer that exerts a significant cardioprotective effect in the clinic; however, the specific mechanisms are not fully understood. Purpose We mainly investigated the protective effects of Tan IIA on doxorubicin (DOX)-induced HF. Methods In an in vitro study, H9C2 and HL-1 cells were cultured and treated with DOX and Tan IIA for 24 h, we investigated the mechanism underlying Tan IIA-mediated protection. In an in vivo study, a model of DOX-induced HF was established in C57BL/6 mice that were divided into the six groups randomly: a control group, a DOX group, DOX groups treated with Tan IIA (DOX+Tan IIA) at dosages of 2.5, 5 and 10 mg/kg/day and DOX groups treated with N-acetylcysteine (NAC) at dosages of 200 mg/kg/day. Result The results demonstrated that Tan IIA significantly increased cell viability and protected against DOX-induced apoptosis. RNA-sequencing showed that the genes expression associated with the apoptotic signaling pathway was altered by Tan IIA. Among the differentially expressed genes, death-domain associated protein (DAXX), which plays an critical role in apoptotic signaling, exhibited increased expression under Tan IIA treatment. In addition, RNA interference was used to silence the expression of DAXX, which abolished Tan IIA-mediated protection against DOX-induced apoptosis; this effect was associated with extracellular signal-regulated protein kinase 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) expression. In the in vivo study, the echocardiography results revealed that heart function was rescued by Tan IIA, and the histomorphology results showed that Tan IIA prevented myocardial structural alteration and myofibril disruption. Furthermore, Tan IIA induced the expressions of DAXX, p-ERK1/2 and p-MEK. Tan IIA also inhibited apoptosis by suppressing the expression of cleaved caspase-8, p-P38 and cleaved caspase-3. Conclusion Our results provide novel interpretations into the important role of DAXX in DOX-induced cardiotoxicity and show that Tan IIA may be a novel agent strategy for HF treatment via activating the DAXX/MEK/ERK1/2 pathway.
研究领域:
心脏病学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 11
·6003-6010
·
IF 3.049
Xian-Ling Yang,Xiu Xing,Jun Li,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
Although functional aliphatic polycarbonates (APCs) have attracted prominent research interest as stimuli-responsive biomaterials, the majority of functional APCs are fabricated by detrimental organometallic catalysts or organo-catalysts. Herein, a facile synthetic strategy based on enzymatic polymerization was developed to construct a selenium-containing amphiphilic aliphatic polycarbonate (mPEG-b-CMP45). Specifically, the selenium in its backbone framework underwent a hydrophobic–hydrophilic transition upon exposure to the abnormal ROS level of the tumor, thus providing a promising platform for ROS-triggered drug release. This amphiphilic mPEG-b-CMP45 efficiently encapsulated doxorubicin (DOX) via self-assembly in aqueous solution and showed an excellent ability to regulate the release of DOX in response to H2O2 at biologically relevant concentrations (100 μM). These DOX-loaded nanoparticles could easily be internalized into U87 cells and possess the inherent antitumor properties of DOX, while they exhibited much lower cytotoxicity in normal cells HL-7702. Moreover, in many cases, the introduction of selenium caused high cytotoxicity of the materials, but the cytotoxicity results in HL-7702 cells demonstrated the good biocompatibility of mPEG-b-CMP45. These collective data suggested the potential use of mPEG-b-CMP45 as a biocompatible and smart drug delivery vehicle.
研究领域:
材料科学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2015
·Vol. 29
·期 11
·533-543
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IF 1.925
Xiaoyan Liu,Yanqiu Liu,Mengchun Cheng,Hongbin Xiao
ABSRACT The present study was undertaken to investigate the metabolic responses of human liver cells HL-7702 on chemicals purified from traditional Chinese medicine: emodin, triptolide, and aristolochic acid. Cytotoxicity tests demonstrated a dose-dependent toxic effect of emodin, triptolide, and aristolochic acid on HL7702 cells for 48 h. Emodin (14 μM), aristolochic acid (12 μg/mL), or triptolide (18 nM) was individually administrated to HL7702 and cell samples were collected after 48 h for metabolites extraction and analysis. Pattern recognition analysis reflected the significant difference in metabolic profiles between chemical-treated groups and the control group. Finally, eight metabolites including N 1 -acetylspermidine, Glu Gly, N -undecanoylglycine, C 16 sphinganine, sphinganine, glutathione, l -palmitoylcarnitine, and elaidic carnitine were detected as potential common biomarkers. Three pathways including sphinganine metabolism, fatty acid oxidation, and oxidative stress were identified. Our findings indicated that metabolomics would be an efficient approach to understand the molecular mechanism of hepatotoxicity induced by chemicals.
研究领域:
药理学
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毒理学
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代谢组学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Boyang Cheng,Xindang Chu,Ruiwen Liu,Xinyuan Ma,Mengyang Wang,Jiayi Zhang,Pingxuan Jiao,Qianqian Gao,Wenxiao Ma,Yongmin Zhang,Chuanke Zhao,Demin Zhou,Sulong Xiao
Betulinic acid (BA) and oleanolic acid (OA) are plant-derived conjugates found in various medicinal plants that have emerged as potential antitumor agents. Herein, a series of novel BA and OA derivatives were synthesized by conjugation with per-O-methylated-β-cyclodextrin (PM-β-CD), and their anticancer properties against a panel of three human cancer cell lines were evaluated. Two OA-PM-β-CD conjugates (48 and 50) were observed to be the most potent conjugates against the three cell lines (MCF-7, BGC-823, and HL-60), with a 15- to 20-fold decrease in the IC50 values (IC50: 6.06–8.47 μM) compared with their parental conjugate (OA). Annexin V-FITC/propidium iodide staining and Western blot analysis revealed that both conjugates induced apoptosis in HL-60 cells. Additionally, in the representative conjugate 48-treated HL-60 cells, a decrease in mitochondrial membrane potential and subsequent release of cytochrome c into the cytosol were observed, indicating the activation of the intrinsic apoptosis pathway. Furthermore, 48 dramatically induced the generation of reactive oxygen species (ROS) in HL-60 cells, and the corresponding effect could be reversed using the ROS scavenger N-acetylcysteine. Collectively, these results suggest that the novel pentacyclic triterpenoid derivatives trigger the intrinsic apoptotic pathways via the ROS-mediated activation of caspase-3 signaling, inducing cell death in human cancer cells.
研究领域:
药理学
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肿瘤学
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药物化学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Junjie Wang,Hui Zhou,Yang Li,Yeshu Mu,Jinghua Li,Chen Hong,Wen Luo
A novel series of benzo[ cd ]indol-2(1 H )-one-donepezil (BIO-DPZ) hybrids (5a-m, 6a-k) was designed, synthesized and evaluated as cholinesterase inhibitors and living cell imaging agents. These compounds were potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compound 6a exhibited the strongest inhibitory activity against AChE with an IC 50 value of 0.16 μM. Compound 6i had the strongest inhibition of BuChE with an IC 50 value of 5.37 μM. Kinetic and molecular modeling studies showed that 6a bound both catalytic active site and peripheral anionic site of AChE. Compounds 6a and 6i both showed lower SH-SY5Y, HepG2 and HL-7702 cytotoxicity than the mitoxantrone. Promisingly, the most active compound, 6a, was successfully used in living SH-SY5Y cell imaging and had predictable lipophilicity and blood-brain-barrier permeation properties. These hybrids should undergo further systematic study in the treatment of Alzheimer's disease.
研究领域:
药理学
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神经科学
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药物化学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）