International Journal of Nanomedicine (Apr 2019)
Characterization and bioactivity of self-assembled anti-angiogenic chondroitin sulphate-ES2-AF nanoparticle conjugate
Abstract
Liang Xing,1,2,* Feng Sun,1,2,* Zhendong Wang,1,2 Yan Li,1,2 Zhifang Yang,1,2 Fengshan Wang,1,3 Guangxi Zhai,3 Haining Tan1,2 1National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, People’s Republic of China; 2Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan 250012, Shandong, People’s Republic of China; 3School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, People’s Republic of China *These authors contributed equally to this work Background: In the past few years, significant progress has been made in inhibiting neovascularization at the tumor site, cutting off the nutrient supply of the tumor, and inhibiting tumor growth and metastasis. However, many proteins/peptides have the disadvantage of poor stability, short half-life, and uncertain targeting ability. Chemical modification can be used to overcome these disadvantages; many polyethylene glycol-modified proteins/peptides have been approved by US FDA. The purpose of this study was to obtain a novel anti-angiogenic chondroitin sulfate (CS)-peptide nanoparticle conjugate with efficient anti-neovascularization and tumor targeting ability and an acceptable half-life. Materials and methods: The CS-ES2-AF nanoparticle conjugate was synthesized and characterized using 1H-nuclear magnetic resonance spectroscopy, transmission electron microscopy, and particle size and zeta potential analyzer. The anti-angiogenic ability was studied using MTT, migration, tube formation, and chick chorioallantoic membrane assays. The targeting ability of CS-ES2-AF was studied by ELISA, surface plasmon resonance, and bioimaging. The pharmacokinetics was also studied.Results: The CS-ES2-AF could self-assemble into stable nanoparticles in aqueous solution, which significantly enhances its anti-neovascularization activity, tumor targeting more explicit, and prolongs its half-life.Conclusion: CS is an effective protein/peptide modifier, and CS-ES2-AF displayed good potential in tumor targeting therapy. Keywords: chondroitin sulfate, ES2-AF, nanoparticles, anti-angiogenesis, targeting
