National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, People's Republic of China,
Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan 250012, Shandong, People's Republic of China,
Int J Nanomedicine. 2019 Apr 10;14:2573-2589. doi: 10.2147/IJN.S195934. eCollection 2019.
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.
The CS-ES2-AF nanoparticle conjugate was synthesized and characterized using H-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.
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.
CS is an effective protein/peptide modifier, and CS-ES2-AF displayed good potential in tumor targeting therapy.
在过去的几年中，在抑制肿瘤部位的新生血管形成、切断肿瘤的营养供应以及抑制肿瘤生长和转移方面取得了重大进展。然而，许多蛋白质/肽类具有稳定性差、半衰期短和靶向能力不确定等缺点。化学修饰可用于克服这些缺点；许多聚乙二醇修饰的蛋白质/肽类已被美国 FDA 批准。本研究旨在获得具有高效抗血管生成和肿瘤靶向能力以及可接受半衰期的新型抗血管生成硫酸软骨素（CS）-肽纳米颗粒缀合物。
使用 H-核磁共振波谱、透射电子显微镜和粒径和 zeta 电位分析仪对 CS-ES2-AF 纳米颗粒缀合物进行了合成和表征。通过 MTT、迁移、管形成和鸡胚尿囊膜试验研究了抗血管生成能力。通过 ELISA、表面等离子体共振和生物成像研究了 CS-ES2-AF 的靶向能力。还研究了药代动力学。
CS-ES2-AF 可在水溶液中自组装成稳定的纳米颗粒，显著增强了其抗血管生成活性，肿瘤靶向更明确，并延长了其半衰期。
CS 是一种有效的蛋白质/肽类修饰剂，CS-ES2-AF 在肿瘤靶向治疗中显示出良好的潜力。
