载蟾毒灵新型“触发式”自组装蛋白聚合物纳米载体的设计制备及肝肿瘤靶向研究

项目名称： 载蟾毒灵新型“触发式”自组装蛋白聚合物纳米载体的设计制备及肝肿瘤靶向研究

项目编号： No.81202930

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 许颖

作者单位： 江苏大学

项目金额： 23万元

中文摘要： 蟾毒灵是蟾酥中抗肿瘤作用最强的有效成分之一，对肝肿瘤细胞有很强的抑制作用。为降低蟾毒灵的毒副作用，增强其肿瘤靶向性，本项目以脂蛋白结构为模型，设计构建以修饰蛋白为亲水外壳（实现血液稳定及肿瘤靶向性），以PBCA纳米粒为内核（更有效的包载难溶性单体蟾毒灵）的新型蛋白聚合物纳米载体。整个载体的构建具有"触发式"特点，一体化完成载药、PBCA聚合及蛋白包覆的载体组装过程，实现对难溶性中药单体的有效包载。对载体的各种理化性质及载体表面结构特征等进行表征，并对载体的肿瘤细胞摄取机制和靶向机制等问题在细胞生物学水平进行深入探讨。尝试探索蛋白靶基密度与载体在血液循环系统中的稳定性和靶向性的量化关系，解决载体的靶向性和体内稳定性最佳平衡设计等共性问题，为靶向载体的设计提供量化依据和指导。本项目将先进的制剂技术和研究方法应用于活性单体的包载和转运，期望能为中药单体的制剂研究提供一个新的思路和方向。

中文关键词： 蟾毒灵；蛋白聚合物纳米载体；“触发式”自组装；抗肿瘤；靶向

英文摘要： Bufalin is one of the major anti-tumor components of the toad venom and has excellent inhibition effect on hepatoma cells. In order to reduce the bufalin toxicity and enhance its tumor targeting effect, we design the novel protein-polymer nanoparticle modeled after the structure of lipoprotein, which has a hydrophilic shell composed of modified protein ( conferred blood stability and tumor targeted) and a core prepared by PBCA nanoparticle ( encapsulate the insoluble active constituent bufalin more effectively). The assembly of the carrier had the trigger characteristic, which can accomplish the drug loading, PBCA polymerization and protein coating automatically. We plan to characterize the physical and chemical properties and the surface structural features of the carrier, and investigate the tumor cell uptake mechanism and target mechanism in depth. We attempt to explore the quantitative relationship between the density of protein and targeted groups with the blood stability and tumor targeting effect of the carrier, which can provide the quantitative basis and guiding significance for the design of targeted carrier. This project applied the advanced formulation technology and research techniques to the drug loading and transportation of the active composition, which may supply a new direction for the pharmace

英文关键词： bufalin；protein-polymer nanoparticle；“trigger” assembly；antitumor；targeted delivery