Marine Drugs
·
2025
·Vol. 23
·期 1
·22
·
IF 5.4
Xia Zheng,Xiaofei Liu,Zhuo Wang,Rui Li,Qiaoli Zhao,Bingbing Song,Kit-Leong Cheong,Jianping Chen,Saiyi Zhong
Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (Na2SeO3) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor.
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
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2022
·
IF 3.682
Juan Wu,Xi Wang,Binglong Zhu,Qinting He,Yaheng Zhang,Wei Jiang
As one of the well-known anticancer drugs, methotrexate (MTX) has been limited in clinical application due to its side effects on normal tissues. This study focused on the one-step hydrothermal synthesis and in vitro evaluation of Fe3O4/RGO-PEI as MTX carriers for targeted anticancer therapy. In which, the Fe3O4 provided magnetic response properties; RGO acted as a stage for Fe3O4 loading and improved the dispersion of Fe3O4; polyethylenimine (PEI) was used as a surface modifier and a storehouse for MTX. The prepared Fe3O4/RGO-PEI nanocomposites exhibited a suitable size, good stability and magnetic responsibility. And the MTX loading content and loading efficiency were calculated to be 26.6% and 90.5%, respectively. What’s more, due to the diffusion and dissolution of PEI, the Fe3O4/RGO-PEI-MTX exhibited excellent pH-sensitivity, the values of MTX release rate (%) within 48 h at pH 5.8 and 4.0 were 64.3% and 87.4%, respectively. Furthermore, MTT assays in cancer cells (HepG2) and normal cells (HUVEC) demonstrated that Fe3O4/RGO-PEI-MTX exhibited high anticancer activity while low toxicity to normal cells, and also the Fe3O4/RGO-PEI composites were practically non-toxic. Thus, our results revealed that Fe3O4/RGO-PEI-MTX would be a competitive candidate for targeted delivery and controlled release of MTX.
研究领域:
材料科学
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纳米技术
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药学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 7
·2571-2583
·
IF 6.843
Qingqing Li,Xianwei Yang,Peipei Zhang,Fei Mo,Peiru Si,Ximeng Kang,Menghan Wang,Jiye Zhang
Corneal neovascularization (CNV) is one of the most important causes of visual impairment worldwide. Dasatinib, a poorly water-soluble tyrosine kinase inhibitor with dual Src family kinase and platelet derived growth factor receptor inhibiting capability, has great potential in the treatment of CNV. In this study, dasatinib was successfully encapsulated into a nanostructured lipid carrier (Dasa-NLC) and the size was approximately 78 nm with a small polydispersity index. The NLC increased the solubility of dasatinib by more than 1220 times, sustained the drug release, reduced the ocular toxicity and facilitated its penetration into the cornea. Dasa-NLC significantly inhibited the proliferation, migration and tube formation of HUVEC cells, the three most important angiogenesis-related cellular changes of the CNV. Next, the in vivo anti-CNV effect of Dasa-NLC was evaluated using an alkaline burned mice CNV model, in which the development of the CNV and pathological changes of the cornea were significantly inhibited. The immunohistochemistry analysis indicated that Dasa-NLC could inhibit both the expression and activation of Src family kinase, a key component in the angiogenesis cascade. Therefore, Dasa-NLC showed considerable promise in the treatment of CNV.
研究领域:
药理学
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眼科学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2022
·Vol. 17
·期 1
·1-17
·
IF 4.546
Yi Qingqing,Liang Pengchen,Liang Dongyu,Cao Liou,Sha Shuang,Jiang Xinquan,Chang Qing
Background Microarc oxidation (MAO) on the surface of medical pure titanium can improve its histocompatibility, and loading drugs on the surface can resist excessive intimal hyperplasia.Methods In this study, salidroside (SAL) was loaded on the surface of porous titanium (Ti) with polydopamine (PDA) carrier. The effects of SAL on the osteogenesis and angiogenesis of Ti implants were studied by phalloidin staining, alizarin red staining, ALP staining, wound-healing assay, cell transwell assay, matrigel tube formation, and osteogenic and angiogenic genes and proteins expression detected by PCR and western blot in vitro. The bone defect model experiments in rats was established in vivo including X-ray, micro CT, hematoxylin and eosin staining (HE), immunohistochemistry (IHC), Goldner's trichrome analysis, Safranin O-fast green staining and determination of contents of TNF-α and IL-6 in serum.Results EDS and EDS mapping showed that SAL could be loaded on the surface of the MAO coating by PDA. A drug release experiment showed that SAL loaded on the Ti coating could release slowly and stably without sudden release risk. In vitro cell experiments showed that the SAL coating could promote the proliferation, morphology, calcification and alkaline phosphate activity of MC3T3-E1 cells. At the same time, it promoted the migration and tube formation of HUVEC cells. The SAL coating promoted osteogenesis and angiogenesis by promoting the expression of genes and proteins related to. In vivo experiments, HE and IHC showed that SAL significantly promoted the expression of COL-1 and CD31. Goldner's trichrome and Safranin O-fast green staining showed that SAL coating could increase the new bone tissue around the implantation site. The SAL coating had anti-inflammatory activity by reducing the levels of TNF-α and IL-6 in vivo.Conclusion Therefore, SAL could improve osteogenesis and angiogenesis in conjunction with the Ti-PDA coating.
研究领域:
生物材料
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组织工程
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骨科
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药剂学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
·
IF 5.268
Wei Liu,Xingtong Dong,Han Qin,Lei Sui,Jian Wang
The guided bone regeneration (GBR) membrane is intended to provide sufficient space for alveolar bone regeneration and meanwhile prevent the invasion of gingival epithelium. In this study, three-dimensional porous reduced graphene oxide/hydroxyapatite (3D rGO/HA) membrane with two different sides was prepared using a two-step electrochemical method. One side of this composite membrane facing the bone defect was formed by 3D porous rGO with HA deposited on the frame of the 3D structure, and the other side of the membrane presented a dense 2D rGO surface to prevent the invasion of the gingival epithelium. The morphology, phase composition, and physical properties of the 3D rGO/HA composite membrane were characterized. Then the cell morphology, viability, and proliferation of pre-osteoblasts (MC3T3-E1 cells) on the 3D porous structure surface of membranes were evaluated and alkaline phosphatase (ALP) secretion as an indication of osteogenic differentiation was also investigated. Meanwhile, cell morphology, viability, and proliferation of HUVEC and L929 cells on the dense structure surface were examined. Finally, a cranial defect model of rat was employed to evaluate the effect of 3D rGO/HA as a GBR membrane in vivo. The results revealed the 3D rGO/HA membrane had good biocompatibility for MC3T3-E1 and HUVEC cells and could significantly enhance ALP secretion. Furthermore, this membrane also promoted the repair of calvarial defects in vivo . These results demonstrated that 3D porous rGO/HA composite membrane with a porous side and another dense side represents great application potential as an ideal GBR membrane.
研究领域:
生物材料
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组织工程
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生物医学工程
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骨科
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牙科材料
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2022
·
IF 7.088
Xing-Rong Wang,Shuai Wang,Hong-Xia Mu,Kai-Yan Xu,Xue-Ting Wang,Jian-Tao Shi,Qi-Hang Cui,Li-Wen Zhang,Shi-Wu Chen
VEGFR-2 is an attractive therapeutic target for antitumor drug research by blocking tumor angiogenesis and PROTAC provides a new technology for targeted protein knockout. Herein, a library of novel VEGFR-2-PROTAC degraders were rationally designed and synthesized based on the Lys residue region on the surface of VEGFR-2 protein using protein structure-based drug design strategy. Among them, P7 exhibited preferable antitumor activity against HGC-27 cells and less toxic to human normal HUVEC, HEK293T and GES-1 cells in vitro , as well as the potent degradation activity of VEGFR-2 protein in HGC-27 cells (DC 50 : 0.084 ± 0.04 μM, D max : 73.7%) and HUVEC cells (DC 50 : 0.51 ± 0.10 μM, Dmax: 76.6%). Additionally, P7 degraded VEGFR-2 protein by the formation of ternary complex and the ubiquitin proteasome pathway in HGC-27 cells. Furthermore, P7 shortened the half-life of VEGFR-2 protein synthesis and had no inhibitory effect on the expression of VEGFR-2 mRNA in HGC-27 cells. Moreover, P7 inhibited the colony formation, migration and invasion of HGC-27 cells in a time- and dose-dependent manner, and meanwhile induced G 2 /M phase cycle arrest and apoptosis . All the results demonstrated that P7 could be as a promising VEGFR-2-PROTAC degrader for gastric cancer therapy.
研究领域:
肿瘤学
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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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2023
·
IF 6
Pu Li,Qiang Liu,Zhenni Xiang,Jian Wang,Wan-Xia Wu,Wen-Jing Yi
The reactive oxygen species (ROS) responsive amphiphilic poly(ethylene glycol)- b -poly(thioketal) (mPEG- b -PTK) copolymer was synthesized by enzyme-catalyzed polymerization for the first time. Core crosslinked (CCL) micelles were prepared via thiol-ene click reaction between the double bond of the side chain of mPEG- b -PTK and the thiol group of pentaerythritol tetrakis (3-mercaptopropionate) as a crosslinker under UV light. The success of crosslinking was verified by NMR and IR. CCL micelles showed better stability in stability against dilution and storage stability experiments compared with the uncrosslinked (UCL) micelles. The ROS-responsiveness of CCL micelles was characterized by DLS, TEM, NMR, AFM and SEM. In vitro release studies, CCL micelles encapsulating doxorubicin (DOX) showed a faster release rate of nearly 100% within 32 h in PBS containing 5 mM H 2 O 2 compared to the control without H 2 O 2 . Cytotoxicity test demonstrated good biocompatibility of CCL micelles and low toxicity with cell viability above 82% and 86% in HeLa cells and HUVEC cells, respectively. And CCL DOX-loaded micelles exhibited great anticancer activity with IC 50 value about 4.8 mg/L for Hela cells. Finally, flow cytometry and confocal laser scanning microscope (CLSM) showed that DOX-loaded micelles had excellent internalization efficiency in HeLa cells. The obtained ROS-responsive CCL micelles held promise for anticancer drug delivery.
研究领域:
药学
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材料科学
·
生物医学工程
·
化学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）