基于净电荷可逆调节的微环境敏感型细胞穿膜肽在两亲性载体材料功能化设计中的应用

项目名称： 基于净电荷可逆调节的微环境敏感型细胞穿膜肽在两亲性载体材料功能化设计中的应用

项目编号： No.81501579

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 孙春萌

作者单位： 中国药科大学

项目金额： 18万元

中文摘要： 缺乏特异性是限制细胞穿膜肽(cell-penetrating peptides, CPPs)发展及临床应用的最主要因素。一直以来，研究人员尝试通过多种手段对CPPs赋予靶向性，但至今仍未有突破性进展。近年来，一种pH敏感的组氨酸-谷氨酸（HE）多肽重复序列被报道可用于调控CPPs的穿膜活性，这种基于不同pH条件下净电荷能够可逆调节的重组多肽HE-CPP被证明可以实现生物大分子的肿瘤靶向性传递。本课题将以HE-CPP的构建理论为基础，同时选用一种常见的两亲性载药系统(mPEG-PLA)为模型，旨在通过载体设计构建一系列具有不同递药机制和释药机制的pH敏感型药物传输系统，达到控制药物释放、提高药物摄取、实现肿瘤靶向性、减少毒副反应等效果，并进一步指导功能多肽设计在一般药物载体中的应用。

中文关键词： 细胞穿膜肽；聚合物胶束；pH敏感；聚乙二醇聚乳酸；电荷调节

英文摘要： Lack of specificity is the major obstacle of cell-penetrating peptides (CPPs) for clinical applications. Many approaches have been investigated to confer CPPs with the property of specific accumulation, but no break-through technology has yet to be achieved. Recent years, we designed a pH sensitive histidine-glutamate acid (HE) repeats which could be used for regulate the activity of cell-penetrating peptides. It has also been verified that recombinant peptide, HE-CPP, with adjustable net charge under different pHs could specifically target the mildly acidic environment at tumor tissue, thereby achieving targeted delivery of biomacromolecules. In this project, a series of pH-sensitive mPEG-PLA-based novel drug delivery systems will be designed and engineered on the basis of the theory of HE-CPP. The novel carriers are expected to have different mechanisms of drug delivery and drug release so as to achieve controlled drug release, increased drug internalization, tumor-targeted drug delivery, reduced toxicity and side-effects. The achivement of this project will be meaningful for the application of functionalized peptides in the modification of normal drug carriers.

英文关键词： Cell-penetrating peptides;Polymer micelles;pH sensitivity;PEG-PLA;charge regulation