Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 17
·3801-3813
·
IF 5.344
Dong Zhou,Sainan Liu,Yongjun Hu,Shiwei Yang,Bing Zhao,Kaikai Zheng,Yuhong Zhang,Peixin He,Guoyan Mo,Yulin Li
Lack of sufficient tumor penetration of the current nanomedicines is a major reason limiting their clinical success in cancer therapy. In this work, we aimed at the development of a novel biodegradable nanoplatform for the selective and controlled delivery of anticancer agents, with improved tumor permeability and the ability to release ultrasmall nanovesicles in the tumor microenvironment. To this end, positively charged nanogels were obtained through the double-crosslinking of chitosan with an ionic physical gelator and a disulfide-containing chemical crosslinker. After conjugation to an anionic oligomer, the cationic nanogels were transformed into negatively charged nanocarriers (CTCP), enabling effective encapsulation of the cationic anticancer agent doxorubicin (DOX) to generate a biodegradable nanomedicine (DOX@CTCP). DOX@CTCP could maintain sustained DOX release and decreased DOX toxicity. Upon arrival at the tumor tissue, the reductive and lysozyme-high microenvironment drives the cleavage of the nanomedicine to release DOX-carrying nanoblocks of smaller size, which together with their acidic-protonable feature achieves an effective therapeutic delivery into cancer cells. The nanomedicine described here showed excellent biocompatibility/biosafety and enhanced in vivo antitumor efficacy.
研究领域:
生物医学工程
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肿瘤学
·
药剂学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Yuling Su,Lili Zhao,Fancui Meng,Quanxin Wang,Yongchao Yao,Jianbin Luo
In order to improve the antibacterial activities while decrease the cytotoxity of silver nanoparticles, we prepared a novel nanocomposites composed of silver nanoparticles decorated lipase-sensitive polyurethane micelles (PUM-Ag) with MPEG brush on the surface. The nanocomposite was characterized by UV–vis, TEM and DLS. UV–vis and TEM demonstrated the formation of silver nanoparticles on PU micelles and the nanoassembly remained intact without the presence of lipase. The silver nanoparticles were protected by the polymer matrix and PEG brush which show good cytocompatibility to HUVEC cells and low hemolysis. Moreover, at the presence of lipase, the polymer matrix of nanocomposites is subject to degradation and the small silver nanoparticles were released as is shown by DLS and TEM. The MIC and MBC studies showed an enhanced toxicity of the nanocomposites to both gram negative and gram positive bacteria, i.e. E. coli and S. aureus , as the result of the degradation of polymer matrix by bacterial lipase. Therefore, the nanocomposites are biocompatible to mammalian cells cells which can also lead to activated smaller silver nanoparticles release at the presence of bacteria and subsequently enhanced inhibition of bacteria growth. The satisfactory selectivity for bacteria compared to HUVEC and RBCs make PUM-Ag a promising antibacterial nanomedicine in biomedical field.
研究领域:
材料科学
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生物医学工程
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Huicong Zhou,Huanjiao Sun,Shixian Lv,Dawei Zhang,Xuefei Zhang,Zhaohui Tang,Xuesi Chen
Traditional chemotherapy strategy exists undesirable toxic side-effects to normal tissues due to the low selectively to cancer cells of micromolecule cytotoxic drugs. One considered method to realizing the targeted delivery and increasing the specificity to tumor tissues of the cytotoxic drug is to transporting and discharging it through an environment-sensitive mechanism. In this study, a novel enzyme-sensitive polymer-doxorubicin conjugate was designed to delivery chemotherapeutic drug in a tumor-specific behavior and selectively activated in tumor tissue. Briefly, doxorubicin (DOX) was conjugated to carboxyl-terminated 4-arm poly(ethylene glycol) through a tetrapeptide linker, alanine-alanine-asparagine-leucine (AANL), which was one of the substrates of legumain , an asparaginyl endopeptidase that was found presented in plants, mammals and also highly expressed in human tumor tissues. Hereinafter, the polymer-DOX conjugate was termed as 4-arm PEG-AANL-DOX. Dynamic laser scattering (DLS) and transmission electron microscopy (TEM) measurements indicated that the 4-arm PEG-AANL-DOX could self-assemble into micelles in aqueous solution. Drug release and in vitro cytotoxicity studies revealed that the 4-arm PEG-AANL-DOX could be cleaved by legumain. Ex vivo DOX fluorescence imaging measurements demonstrated that the 4-arm PEG-AANL-DOX had an improved tumor-targeting delivery as compared with the free DOX·HCl. In vivo studies on nude mice bearing MDA-MB-435 tumors revealed that the 4-arm PEG-AANL-DOX had a comparable anticancer efficacy with the free DOX·HCl but without DOX-related toxicities to normal tissues as measured by body weight change and histological assessments, indicating that the 4-arm PEG-AANL-DOX had an improved therapeutic index for cancer therapy. Statement of Significance Herein we describe the construction of a novel tumor environment-sensitive delivery system through the instruction of a legumain-cleavable linkage to a polymer-DOX conjugate (4-arm PEG-AANL-DOX). This particular design strategy allows for polymer-DOX conjugates to be delivered in a tumor-specific manner and selectively activable in tumor microenvironment so that it can combine the advantages of tumor-specific delivery and tumor intracellular microenvironment-triggered release systems.
研究领域:
药学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2014
·Vol. 5
·期 12
·9130-9137
·
IF 3.708
Jiahuan Lei,Yu Liu,Xinyu Wang,Pan Hu,Xinsheng Peng
Au nanoparticles/mesoporous CuO nanosheets were successfully synthesized by the assembly of negatively charged AuCl4−1 and positively charged CuO nanosheets using sodium citrate and thermal reduction, respectively. The structure and morphology were characterized in detail. Both the loading amount of Au nanoparticles and the performance were controlled by the reduction process. The resulting Au/CuO NSs exhibited good catalytic activity for CO oxidation and good non-enzymatic sensitivity for glucose.
研究领域:
材料科学
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化学
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生物传感
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催化反应
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Debin Yang,Tingfang Wang,Zhigui Su,Lingjing Xue,Ran Mo,Can Zhang
A multistimuli responsive drug delivery system (DDS) based on sulfhydryl and amino-cofunctionalized mesoporous silica nanoparticles (SH/NH2-MSNs) has been developed, in which the multifunctional hyaluronic acid (HA) derivatives were grafted onto the SH/NH2-MSNs by disulfide bonds for targeting delivery, controlling drug release and reversing multidrug resistance (MDR). The doxorubicin (Dox) loaded multifunctional HA derivatives modified mesoporous silica nanoparticles (Dox/HHS-MSNs) were enzyme and redox sensitive, which could respond to the intracellular stimuli of hyaluronidase (HAase) and glutathione (GSH) successively and prevent drug leakage before reaching the tumor tissues. The cellular uptake experiments showed that Dox/HHS-MSNs were vulnerable to be endocytosed into the Dox-resistant human breast adenocarcinoma (MCF-7/ADR) cells, efficiently realized the endolysosomal escape and remained in the cytoplasm. Because of orchestrating multiple actions above including active targeting, endolysosomal escape and efficient multilevel drug release, Dox/HHS-MSNs could induce the strongest apoptosis and cytotoxicity of MCF-7/ADR cells. Furthermore, a series of in vivo studies on MCF-7/ADR tumor-bearing xenograft mouse models demonstrated that Dox/HHS-MSNs possessed the enhanced tumor-targeting capacity and the best therapeutic efficacy to reverse cancer MDR.
研究领域:
药学科学
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纳米技术
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癌症研究
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药物递送系统
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2022
·
IF 6.056
Qibin Li,Quanyi Chen,Yueying Wu,Zhibao Chen,Ying Liu,Zhijia Fang,Qi Deng
The bacteriocin CAMT6 is a novel bacteriocin produced by Enterococcus durans YQ-6 isolated from Larimichthys polyactis in the South China Sea. In this study, the bacteriocin CAMT6 was purified by extraction using ethyl acetate, Sephadex LH-20 column chromatography, cation exchange chromatography and reversed-phase high-performance liquid chromatography, in sequence. The Liquid Chromatograph Triple Quadrupole Mass Spectrometer (LC-MS/MS) analysis revealed that the relative molecular mass and amino acid sequence of the bacteriocin CAMT6 were 1254.63 Da and N-GAVHDVKDVLDS, respectively. Combined with the circular dichroism (CD) spectroscopy results, CAMT6 was determined to be a novel Class IId bacteriocin. CAMT6 exhibited broad-spectrum antibacterial activity, inhibiting both gram-negative and gram-positive bacteria, even fungi. CAMT6 exhibited strong temperature stability, was stable over pH 2–7, and was inactivated by proteases. CAMT6 also significantly removed L. monocytogenes biofilms and inhibited L. monocytogenes by disrupting the permeability of the cell membrane. Furthermore, CAMT6 can effectively inhibit the growth of L. monocytogenes in chicken breast. These results suggest that the bacteriocin CAMT6 could serve as a potential biological preservative for food.
研究领域:
微生物学
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食品科学
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生物化学
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产品关联
DOI
高影响因子
JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
·
2018
·Vol. 33
·期 2
·512-523
·
IF 0.524
Zhou Huimin,Gao Yuxiang,Xu Haixing,Li Xin,Lü Yahui,Ma Tian,Cai Xinjie,Li Rui,Wang Xiaobing,Xu Peihu
A multifunctional drug delivery system (GNRs@mSiO 2 -HA-RGD) was developed by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica- coated gold nanorods (GNRs@mSiO 2 ) for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and 1 H NMR. Doxorubicin hydrochloride (DOX), an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO 2 -HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has pH-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO 2 -HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@ mSiO 2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO 2 -HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO 2 -HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2022
·
IF 6.056
Xiangpeng Han,Mengyu Zhang,Jiayi Peng,Jinsong Wu,Qingping Zhong
Vibrio parahaemolyticus and its biofilm threaten food safety and human health. Bacteriocins are known to inhibit various foodborne bacteria and their biofilms; however, few bacteriocins with antibiofilm activity against V. parahaemolyticus have been reported. Herein, a novel plantaricin Z057 from Lactiplantibacillus plantarum Z057 was extracted with ethyl acetate, purified by Sephadex LH-20 gel chromatography and reversed-phase high-performance liquid chromatography, and identified by nano-liquid chromatography coupled with tandem mass spectrometry. Its molecular mass and amino acid composition were 1272.61 Da and A-G-G-D-G-G-H-G-G-S-I-I-L-Y, respectively. Plantaricin Z057 presented a broad antibacterial spectrum against Gram-positive and Gram-negative pathogens. Moreover, it also exhibited excellent heat tolerance, maintained antibacterial activity at pH 2.0–4.0, and was susceptible to common proteases (pepsin, trypsin, papain, proteinase K). In addition, scanning electron microscopy revealed that plantaricin Z057 destroyed membrane integrity and caused cell deformation and cytoplasmic leakage. The crystal violet staining and XTT reduction assays revealed that plantaricin Z057 markedly decreased biofilm biomass and metabolic activity of V. parahemolyticus . Fluorescence microscopy showed that plantaricin Z057 efficiently inactivated sessile cells, and damaged integrated biofilm structure by reducing the extracellular polymer content. In summary, plantaricin Z057 exhibited significant potential for controlling V. parahaemolyticus and could be used in food production as a biological preservative.
研究领域:
微生物学
·
食品科学
·
生物技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）