Author: Xing, Liang; Sun, Feng; Wang, Zhendong; Li, Yan; Yang, Zhifang; Wang, Fengshan; Zhai, Guangxi; Tan, Haining
Title: Characterization and bioactivity of self-assembled anti-angiogenic chondroitin sulfate-ES2-AF nanoparticle conjugate Document date: 2019_4_10
ID: x8f598x2_45
Snippet: Studies have shown that ES could stably bind to the precursor protein of matrix metalloproteinase to form a complex, 47 blocking the activation and catalytic ability of matrix metalloproteinases, whereas matrix metalloproteinases could create necessary conditions for cell migration by dissolving the extravascular matrix. ES2, as the main active fragment of ES, also has the ability to stably bind to the precursor proteins of matrix metalloproteina.....
Document: Studies have shown that ES could stably bind to the precursor protein of matrix metalloproteinase to form a complex, 47 blocking the activation and catalytic ability of matrix metalloproteinases, whereas matrix metalloproteinases could create necessary conditions for cell migration by dissolving the extravascular matrix. ES2, as the main active fragment of ES, also has the ability to stably bind to the precursor proteins of matrix metalloproteinase. The results of cell metastasis showed that the activity of CS-ES2-AF in inhibiting cell metastasis was significantly better than unmodified ES2-AF at low concentrations, and there was no significant difference between CS-ES2-AF and ES2-AF at high concentration. In agreement with the results of MTT, the efficiency of CS in improving the solubility of ES2-AF increased at low drug concentration. Therefore, CS-ES2-AF was more efficient in inhibiting endothelial cell metastasis than ES2-AF. When the concentration was increased, the activity of the two drugs was equivalent, which might be due to CS promoting the adhesion and growth of endothelial cells to counteract the inhibition of ES2-AF at a certain degree. 48 Endothelial cell proliferation and differentiation are the vital parts in neovascularization. Matrigel is a soluble basement membrane matrix that is similar to mammalian cell basement membrane components. 49 Related studies have shown that the matrigel, as an extracellular mechanism complex, added to the cell culture environment could promote cell proliferation, differentiation, and collagen secretion. 50 Notes: Mice received a single intravenous injection of es2-aF or cs-es2-aF, with a dose of es2-aF at 20 mg/kg. The results are shown as mean ± sD (n=5). Abbreviations: c max , the maximum plasma concentration of es2-aF and cs-es2-aF; t 1/2 , half-life of es2-aF and cs-es2-aF in plasma; MrT 0→t , average residence times in vivo; T max , the time to reach maximum plasma concentration; aUc, area under the curve for the plasma concentration versus time curve of es2-aF and cs-es2-aF.
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