联合转运siRNA/阿霉素的蛋白纳米笼抗肿瘤药物载体研究

项目名称： 联合转运siRNA/阿霉素的蛋白纳米笼抗肿瘤药物载体研究

项目编号： No.51503003

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 一般工业技术

项目作者： 关新刚

作者单位： 北华大学

项目金额： 20万元

中文摘要： 纳米抗肿瘤药物是近年抗肿瘤研究的热门话题。小干扰RNA（siRNA）和小分子化疗药共转运的纳米载药体系是最具潜力的有效肿瘤治疗方案之一。蛋白纳米笼是特定蛋白通过多个亚基组装形成的中空球状复合体，近年来在利用其特殊结构及理化特性用于构筑肿瘤成像和药物转运体系方面取得了重要进展。然而，截至目前非病毒类蛋白纳米笼的药物转运几乎仅限于阿霉素。拓展蛋白纳米笼的药物担载类型、开发新转运功能是当前面临的一项难题。本申请项目拟通过表达纳米笼蛋白-阳离子多肽融合蛋白制备阳离子多肽蛋白纳米笼，利用阳离子多肽高效复合siRNA的特性，探索开发基于蛋白纳米笼的siRNA高效转运体系，在此基础上利用蛋白纳米笼的特殊理化性能开发siRNA/阿霉素联合转运的具有高安全性、肿瘤靶向、体内长循环、肿瘤微环境敏感等特性的多功能纳米载药体系，本项目对开发设计智能、安全和高效的核酸/化疗药联合载药体系具有重要意义。

中文关键词： 蛋白纳米笼；药物输送；阳离子多肽

英文摘要： Nanomedicines have attracted great attention as effective anti-cancer drugs in recent years. Co-delivery of small interfere RNA (siRNA) and small molecule anti-cancer drugs using nanocarriers is one of the most promising treatment for cancer therapy. Protein nanocages, which are hollow spherical complex assembled by some proteins subunits, have been used in constructing multi-functional tumor imaging and drug delivery system during the past decade. However, drug delivery using non-virus protein nanocages mainly focused on the doxorubicin or photosensitizer, other drugs were rarely reported until now. Exploring new types of loading drug and developing new applications of protein nanocages are greatly needed. In this study we will develop efficient siRNA delivery system by expressing the fusion protein of nanocage protein-cationic polypeptides. Moreover, siRNA/doxorubicin co-delivery systems based on protein nanocages would be developed based on the siRNA delivery by protein nanocages. We expected to acquire an efficient siRNA/doxorubicin co-delivery system with high safety, tumor targeting, long circulation and other characteristics using protein nanocages with cationic polypeptides. This study would be of great significance for development of safe and smart nanocarriers for nucleic acid and small anti-cancer drugs.

英文关键词： protein nanocage;drug delivery;cationic polypeptides