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LWT-FOOD SCIENCE AND TECHNOLOGY · 2021 · IF 4.952

Characterization of fermented soymilk by Schleiferilactobacillus harbinensis M1, based on the whole-genome sequence and corresponding phenotypes

Yin Zheng,Li Li,Zekun Jin,Peipei An,Shang-Tian Yang,Yongtao Fei,Gongliang Liu

The use of Schleiferilactobacillus ( S. ) harbinensis M1 as a starter culture, has been shown to improve the organoleptic quality of fermented soymilk, but its contribution to nutrient transformation and health-related functionality remains unclear. This study characterized the biotransformation of carbohydrates, isoflavones , proteins and free amino acids, as well as the antioxidant and antiproliferative activities of soymilk fermented by S. harbinensis M1. After fermentation, soybean carbohydrates were mainly converted into lactic acid (76.68 mmol/L) and acetic acid (8.19 mmol/L), isoflavone glucosides (daidzin and genistin) were partially converted to aglycones (daidzein and genistein). Soybean proteins were extensively hydrolyzed into oligopeptides and free amino acids, and the soluble peptide fraction (451-189 Da) increased from 4.6% to 86%. Whole-genome sequencing of S. harbinensis M1 revealed a 3,592,195 bp circular chromosome with 53.02% (G + C) content and 3375 coding genes. Metabolic prediction revealed the enzymes required for carbohydrate/pyruvate metabolism and isoflavone biotransformation. The whole proteolytic system was predicted, including peptide transport system and 66 genes encoding proteinases/peptidases. S. harbinensis M1 significantly ( p  < 0.05) improved the antioxidant activity and antiproliferative effects of soymilk against HepG2/MCF-7 cells. These findings suggest that S. harbinensis M1 can be used as a proteolytic starter-culture to make functional fermented foods .

研究领域: 食品科学 · 微生物学 · 基因组学 · 营养学 · 生物化学
✓ 已验证 DOI 高影响因子
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BIOMACROMOLECULES · 2018 · IF 5.738

Lysosome-Independent Intracellular Drug/Gene Codelivery by Lipoprotein-Derived Nanovector for Synergistic Apoptosis-Inducing Cancer-Targeted Therapy

Wei Wang,Kerong Chen,Yujie Su,Jielei Zhang,Min Li,Jianping Zhou

In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, was constructed for codelivery of paclitaxel (PTX) and wild-type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and −20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses. The high p53 protein expression in MCF-7 cells after rHDL-mediated transfection was detected by Western blotting assay. Moreover, PTX-DODAB/p53-rHDL nanoparticles showed superior cytotoxicity and significantly induced apoptosis in SR-BI overexpressed MCF-7 cells. In in vivo studies, PTX-DODAB/p53-rHDL nanoparticles without obvious toxic effects to vessels, blood, or major organs exhibited efficient tumor targeting and encouraging antitumor effects on tumor-bearing nude mice compared with controls. All the results above indicated that PTX-DODAB/p53-rHDL nanoparticles held broad prospects in combination of chemotherapeutics and gene therapeutic agents for cancer-targeted therapy.

研究领域: 药学 · 癌症研究 · 纳米技术 · 分子生物学 · 药物递送系统
✓ 已验证 DOI PubMed 高影响因子
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Polymer Chemistry · 2015 ·Vol. 6 ·期 13 ·2445-2456 · IF 5.52

A reduction-dissociable PEG-b-PGAH-b-PEI triblock copolymer as a vehicle for targeted co-delivery of doxorubicin and P-gp siRNA

Minghui Xu,Junmin Qian,Aili Suo,Ting Liu,Xuefeng Liu,Hongjie Wang

To enhance the therapeutic efficacy of doxorubicin (DOX) to breast cancer cells, a multifunctional triblock copolymer, poly(ethylene glycol)-block-poly(L-glutamic acid γ-hydrazide)-block-polyethylenimine (PEG-b-PGAH-b-PEI) having a cleavable disulfide linkage between blocks, was developed as a vehicle for targeted co-delivery of DOX and P-glycoprotein (P-gp) siRNA into MCF-7/ADR cells. The PGAH blocks were used to chemically conjugate DOX molecules via hydrazone bonds, while the PEI blocks could complex siRNA through electrostatic interactions. A tumor-targeting agent, folic acid (FA), was attached to the distal ends of the PEG blocks to specifically bind to the folate receptors overexpressed in MCF-7/ADR cells. The DOX-conjugated copolymer would self-assemble in aqueous solutions into cationic nanomicelles, which could condense siRNA to form nanomicelleplexes with an average particle size of ∼194 nm and a positive zeta potential of >+10 mV. The nanomicelleplexes exhibited sustained drug release profiles, and the release rates of DOX and siRNA from the nanomicelleplexes in a reductive acidic environment (pH 5.0 + 10 mM glutathione) were much faster than those under physiological conditions (pH 7.4). FA-decorated nanomicelleplexes were more efficiently internalized by MCF-7/ADR cells via folate-receptor-mediated endocytosis and exhibited a higher cytotoxic effect on MCF-7/ADR cells in comparison with FA-undecorated nanomicelleplexes. Furthermore, the synergistic effects of DOX and P-gp siRNA in inhibiting cell proliferation and inducing apoptosis in MCF-7/ADR cells were achieved by the FA-targeted co-delivery system. The triblock copolymer itself had a low cytotoxicity. These results indicate that the triblock copolymer could serve as an ideal tumor-targeting vehicle for simultaneous delivery of drugs and siRNA in breast cancer therapy.

CAS / MDL: 77-58-7
研究领域: 药学 · 纳米技术 · 癌症治疗 · 药物递送系统 · 生物医学工程
✓ 已验证 产品关联 DOI 高影响因子
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Materials Science & Engineering C-Materials for Biological Applications · 2016 · IF 3.42

Biocompatible cationic pullulan-g-desoxycholic acid-g-PEI micelles used to co-deliver drug and gene for cancer therapy

Lili Chen,Fangling Ji,Yongming Bao,Jing Xia,Lianying Guo,Jingyun Wang,Yachen Li

The greatest crux in the combination of chemotherapy and gene therapy is the construction of a feasible and biocompatible carrier for loading the therapeutic drug and gene simultaneously. Here, a new amphiphilic bifunctional pullulan derivative (named as PDP) synthesized by grafting lipophilic desoxycholic acid and low-molecular weight (1   kDa) branched polyethylenimine onto the backbone of pullulan was evaluated as a nano-carrier for the co-delivery of drug and gene for potential cancer therapy. PDP exhibited good blood compatibility and low cytotoxicity in the hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. By self-assembly process, the amphiphilic PDP polymer formed cationic core-shell nanomicelles in aqueous solution with an average diameter of 160.8   nm and a zeta potential of approximate 28   mV. The PDP micelles had relative higher drug encapsulation efficiency (84.05%) and loading capacity (7.64%) for doxorubicin (DOX), an effective anti-tumor drug, demonstrating sustained drug release profile and good DNA-binding ability. The flow cytometry and confocal laser scanning microscopy showed that PDP/DOX micelles could be successfully internalized by MCF-7 cells, and presenting higher cytotoxicity against MCF-7 cells than that of free DOX. Furthermore, PDP micelles could efficiently transport tumor suppressor gene p53 into MCF-7 cells, and the expressed exogenous p53 protein induced MCF-7 cells to die. More excitedly, in comparison with single DOX or p53 delivery, the co-delivery of DOX and gene p53 using PDP micelles displayed higher cytotoxicity, induced higher apoptosis rate of tumor cells and blocked more effectively the migration of cancer cells in vitro . In tumor-bearing mice, co-delivery of DOX and p53 also exhibited enhanced antitumor efficacy as compared with single delivery of DOX or p53 alone. In summary, these results demonstrated that it is highly promising to use cationic PDP micelles for effectively co-delivering functional gene and chemotherapeutic agent, and thus improving antitumor efficacy and systemic toxicity.

研究领域: 药学 · 纳米技术 · 癌症研究 · 生物医学工程 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2016 · IF 7.476

Multienzyme decorated polysaccharide amplified electrogenerated chemiluminescence biosensor for cytosensing and cell surface carbohydrate profiling

Ling Zhang,Yangzhong Wang,Qianqian Tian,Yang Liu,Jinghong Li

A novel ECL biosensor for cytosensing and cell surface carbohydrate expression evaluation was developed, by the integration of the peptide modified interface for highly specific carbohydrate recognition and sodium alginate loaded glucose oxidase as the signal probe with high signal amplification efficiency. A cysteine-terminated peptide self-assembled on the electrode through Au–S bond to construct a functional interface for cell capture, with decent biocompatibility and high affinity for the human breast cancer cell MCF-7. Concanavalin A lectin modified gold nanoparticles specifically recognized the cell surface carbohydrates and were absorbed on the electrode, followed by the immobilization of multiple glucose oxidase conjugated sodium alginate, which could remarkably increase the sensitivity of the biosensor with enhanced catalysis. The as-proposed ECL cytosensor was successfully applied for the detection of the MCF-7 tumor cells, whose glycans on the cell membranes are over-expressed. A low detection limit of 150   cells   mL −1 was obtained, with a wide dynamic linear range from 5.0×10 2 to 5.0×10 5   cells   mL −1 . Due to the excellent sensitivity, stability and biocompatibility, the ECL biosensor would be promising in reliable diagnostics of glycan relevant biomarkers for cancer and other diseases.

CAS / MDL: 6104-58-1 9005-38-3
研究领域: 生物传感器 · 癌症诊断 · 分析化学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2019 · IF 9.518

Integration of fluorescence imaging and electrochemical biosensing for both qualitative location and quantitative detection of cancer cells

Ya Cao,Yuhao Dai,Hong Chen,Yingying Tang,Xu Chen,Ying Wang,Jing Zhao,Xiaoli Zhu

In this work, DNA-templated silver nanoclusters (DNA-AgNCs) with unique fluorescent and electrochemical properties are prepared as dual signal probes for both qualitative imaging and quantitative detection of cancer cells in an integrated system . ITO electrode that has good light transmittance and electric conductivity is employed as a substrate for dual analysis of cancer cells. ITO electrode is firstly modified by AS1141 aptamer , which could selectively bind to nucleolin overexpressed on the surface of a model breast cancer cell, MCF-7 cell line. The composite of mucin 1 antibody (anti-MUC1) and DNA-AgNCs then binds to MUC1 on the surface of captured MCF-7 cell, forming a sandwich-like structure. Therefore, our method allows noninvasive fluorescence imaging and amplified electrochemical detection using a single labeling platform, providing a biocompatible and highly specific method for adequate analysis of cancer cells. Experimental results demonstrate that strong red fluorescence of DNA-AgNCs clearly displays the loading of cancer cells on ITO electrode after dual recognition, and amplified electrochemical signals of DNA-AgNCs enable improved sensitivity toward quantitative analysis with a detection limit of 3 cells.

CAS / MDL: 111-30-8 64987-85-5
研究领域: 生物医学工程 · 分析化学 · 癌症研究 · 纳米技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2019 · IF 4.213

Polymer-lipid hybrid nanoparticles: A novel drug delivery system for enhancing the activity of Psoralen against breast cancer

Manling Du,Yong Ouyang,Fansu Meng,Xingwang Zhang,Qianqian Ma,Yong Zhuang,Hui Liu,Mujuan Pang,Tiange Cai,Yu Cai

A polymer-lipid hybrid nanocarrier was developed to encapsulate psoralen (PSO) to improve its water solubility and bioavailability. The effects of PSO-loaded polymer-lipid hybrid nanoparticles (PSO-PLNs) on breast cancer MCF-7 cells were investigated. PSO-PLNs were prepared through a nanoprecipitation method and were optimized by a central composite design-response surface methodology using particle size and entrapment efficiency as indices. Dynamic light scattering and transmission electron microscopy analysis confirmed the physicochemical characterizations of PSO-PLNs, which had an average size of 93.44 ± 2.39 nm and a zeta potential of −27.63 ± 0.31 mV. In vitro drug release of PSO-PLNs was evaluated using dialysis and showed a delayed release compared with free PSO. The in vivo anticancer efficiency of PSO-PLNs was appreciated using a MCF-7 breast tumor model. Administration of PSO-PLNs showed similar antitumor efficacy but lower toxicity compared with doxorubicin . Our designed nanocarriers successfully optimized the pharmacokinetics of PSO via improved systemic delivery.

CAS / MDL: 9005-65-6
研究领域: 药学 · 纳米技术 · 癌症研究 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Molecular Medicine Reports · 2017 ·Vol. 17 ·期 2 ·2373-2383 · IF 1.692

Novel multi‑kinase inhibitor, T03 inhibits Taxol‑resistant breast cancer

Yan Li,Chunxia Liu,Ke Tang,Yan Chen,Kang Tian,Zhiqiang Feng,Jindong Chen

Activation of kinase-associated signaling pathways is one of the leading causes of various malignant phenotypes in breast tumors. Strategies of drug discovery and development have investigated approaches to target the inhibition of protein kinase signaling. In the current study, the anti‑tumor activities of a novel multi‑kinase inhibitor, T03 were evaluated in breast cancer. T03 inhibited Taxol‑resistant breast cancer cell proliferation and induced cell cycle arrest and apoptosis in vitro and in vivo. The current results demonstrated that T03 downregulated c‑Raf, platelet‑derived growth factor receptor‑β and other kinases, thus inhibited Raf/mitogen‑activated protein kinase kinase/extracellular signal‑regulated kinase and Akt/mechanistic target of rapamycin survival pathways in MCF‑7 and MCF‑7/Taxol xenograft tumors. At a dose of 100 mg/kg, T03 inhibited tumor growth by 62.90 and 59.98% in tumor weight in MX‑1 and MX‑1/T xenograft models, respectively and by 62.60 and 60.22% in MCF‑7 and MCF‑7/T tumors, respectively. These data indicate that the novel multi‑kinase inhibitor, T03, may present as a potential compound to develop novel treatments against breast cancer and Taxol‑resistant breast tumors.

CAS / MDL: 61791-12-6
研究领域: 肿瘤学 · 药理学 · 癌症研究 · 药物开发
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2017 ·Vol. 22 ·期 1 ·171 · IF 2.861

In Vitro DNA-Binding, Anti-Oxidant and Anticancer Activity of Indole-2-Carboxylic Acid Dinuclear Copper(II) Complexes

Xiangcong Wang,Maocai Yan,Qibao Wang,Huannan Wang,Zhengyang Wang,Jiayi Zhao,Jing Li,Zhen Zhang

Indole-2-carboxylic acid copper complex (ICA-Cu) was successfully prepared and characterized through elemental analysis, IR, UV-Vis,1H-NMR, TG analysis, and molar conductance, and its molecular formula was [Cu2(C9H6O2N)4(H2O)2]·2H2O. The binding ability of ICA-Cu to calf thymus DNA (CT-DNA) was examined by fluorescence spectrometry and the viscosity method. The results indicated that, upon the addition of increasing amounts of CT-DNA, the excitation and emission intensity of ICA-Cu decreased obviously and the excitation spectra shifted towards a long wavelength. ICA-Cu could displace ethidium bromide (EB) from the EB-DNA system, making the fluorescence intensity of the EB-DNA system decrease sharply; the quenching constantKSVvalue was 3.99 × 104M−1. The emission intensity of the ICA-Cu-DNA system was nearly constant, along with the addition of Na+in a series of concentrations. The fluorescence of the complex could be protected after the complex interacted with DNA. A viscosity measurement further supported the result that the ICA-Cu complex may interact with DNA in an intercalative binding mode. The antioxidant activities of ICA-Cu were evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, a hydroxyl radical (OH) scavenging assay, and a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay. The ICA-Cu exhibited the highest inhibitory effects on the ABTS radical (94% inhibition at 60 µM), followed by OH and DPPH radicals (the degrees of inhibition being 71% and 56%, respectively). The in vitro cytotoxicity activity of ICA-Cu against two human breast cancer cell lines, MDA-MB-231 and MCF-7, was investigated by 3-[4,5-dimethyltiazol2-yl]-2.5-diphenyl-tetrazolium bromide (MTT) assay and cellular morphological analysis. The results showed that, upon increasing the concentration of ICA-Cu, an increase was observed in growth-inhibitory activity and the inhibition percentage were greater than 90% at 20 µM in both cell lines. Also, cellular morphological changes in the two cell lines agreed with the cytotoxicity results.Keywords:DNA-binding;antioxidant;anticancer;indole-2-carboxylicacid;copper(II) complexes

研究领域: 化学 · 生物化学 · 药理学 · 癌症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2024 · IF 4.9

The preparation of shikonin-based nanomedicine with robust GSH-responsiveness

Zhiyuan Liu,Rui Sun,Yaxuan Huang,Fengyun Xu,Nan Li,Wei Zhang,Pengfei Ge,Wenke Zhang

Shikonin (SHK), an active naphthoquinone pigment isolated from the root of Chinese herbal medicine has been proven to have a significant therapeutic effect on breast cancer. However, the poor water solubility as well as the lack of tumor targeting restrict the practice application of SHK molecules as chemotherapeutic agents. Here, SHK drugs were chemically conjugated to polyethylene glycol (PEG) molecules via a disulfide bond (referred to as SHK-SS-PEG) through a facile one-step strategy. The conjugates exhibited an excellent water solubility of 12.96 mM, which is ca. 7807 times as high as that of pure SHK drugs. Noteworthily, the conjugates can self-assemble into spherical micelles with an average particle size of 106 nm, facilitating in vivo delivery as well as the accumulation in tumor tissues based on the enhanced permeability and retention (EPR) effect. Moreover, the disulfide bond enables rapid cleavage of micelles and efficient release of SHK molecules from the conjugates in response to reduced Glutathione (GSH) overexpressed within tumor cells. Thanks to the GSH-responsiveness release of SHK, the conjugate-based micelles (containing 6 μM SHK) resulted in the cell killing rate of 73 % for the MCF-7 breast cancer cells after 48 h incubation, which is 45 % higher than that for the HUVEC normal cells. All these collective beneficial properties make the SHK-SS-PEG conjugate a promising candidate for the treatment of many types of cancers.

研究领域: 药学 · 纳米技术 · 癌症研究 · 药物递送系统
✓ 已验证 产品关联 DOI 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2015 · IF 3.65

Multifunctional mesoporous silica nanoparticles mediated co-delivery of paclitaxel and tetrandrine for overcoming multidrug resistance

Lejiao Jia,Zhenyu Li,Jingyi Shen,Dandan Zheng,Xiaona Tian,Hejian Guo,Ping Chang

The objective of the study is to fabricate multifunctional mesoporous silica nanoparticles for achieving co-delivery of conventional antitumor drug paclitaxel (PTX) and the multidrug resistance reversal agent tetrandrine (TET) expecting to overcome multidrug resistance of MCF-7/ADR cells. The nanoparticles were facile to prepare by self-assemble in situ drug loading approach. Namely, PTX and TET were solubilized in the cetyltrimethylammonium bromide (CTAB) micelles and simultaneously silica resources hydrolyze and condense to form nanoparticles. The obtained nanoparticles, denoted as PTX/TET-CTAB@MSN, exhibited pH-responsive release property with more easily released in the weak acidic environment. Studies on cellular uptake of nanoparticles demonstrated TET could markedly increase intracellular accumulation of nanoparticles. Furthermore, the PTX/TET-CTAB@MSN suppressed tumor cells growth more efficiently than only delivery of PTX (PTX-CTAB@MSN) or the free PTX. Moreover, the nanoparticle loading drugs with a PTX/TET molar ratio of 4.4:1 completely reversed the resistance of MCF-7/ADR cells to PTX and the resistance reversion index was 72.3. Mechanism research showed that both TET and CTAB could arrest MCF-7/ADR cells at G1 phase; and besides PTX arrested cells at G2 phase. This nanocarrier might have important potential in clinical implications for co-delivery of multiple drugs to overcome MDR.

研究领域: 纳米技术 · 药物科学 · 癌症研究 · 药物递送系统 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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BIOORGANIC & MEDICINAL CHEMISTRY · 2023 · IF 3.5

Development of novel quinoline-NO donor hybrids inducing human breast cancer cells apoptosis via inhibition of topoisomerase I

Guiying Wu,Hui Zhong,Ying Wang,Li Chen,Jianbo Sun

A number of NO-releasing quinoline derivatives have been designed and synthesized by introducing NO donor to quinoline carboxylic acid fragment. The anti-proliferation of all target compounds was evaluated against human cancer cell lines (HCT-116, MCF-7, and A549), MCF-7/ADR and normal cell (MCF-10A). Most compounds showed cytotoxic activity on cancer cells and drug-resistant cells with IC 50 values in the range of 0.62–5.51 μM. Importantly, these compounds showed low toxicity to normal cells (4.21–34.08 μM). Further mechanism studies showed that the most potent compound 9 could release high concentration of NO and inhibit the activity of topoisomerase I. In addition, 9 regulated apoptosis-related proteins, generated ROS and blocked MCF-7 cells in G2/M phase to induce cell apoptosis. Furthermore, the P-gp-mediated transport was also influenced by 9 . And 9 could significantly inhibit the growth of tumor in vivo without observable organ-related toxicities. Overall, as a novel NO-releasing quinoline derivative, 9 was worthy for further in-depth study.

研究领域: 肿瘤学 · 药理学 · 分子生物学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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