响应性聚合物纳米载体稳定性和药物控释/成像性能的同步调控

项目名称： 响应性聚合物纳米载体稳定性和药物控释/成像性能的同步调控

项目编号： No.51473153

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 张国颖

作者单位： 中国科学技术大学

项目金额： 85万元

中文摘要： 理想的基于嵌段聚合物组装体的纳米诊疗体系需同时满足结构稳定以及响应性触发释放药物和成像增强等条件，但稳定性提高与药物触发释放、成像增强等在设计上存在矛盾。针对这一局限性，本项目拟设计合成多种刺激响应性两亲性嵌段共聚物，在疏水嵌段引入可在氧化-还原性环境或光照条件下发生响应性解离的触发基元以保护侧链上的伯氨基团，同时引入可以对微环境变化产生高灵敏度响应的荧光成像基元和磁共振造影剂基元等；基于这类嵌段共聚物构筑兼具药物控释和成像功能的多功能纳米组装体，它们被肿瘤细胞摄入后，发生触发基元的生物环境响应性解离和结构重排并释放出伯氨基团，进而发生分子链间交联反应使组装体的结构稳定性提高，同时组装体疏水微区发生疏水-亲水转变，从而有效调控负载药物的释放并通过荧光和磁共振信号的变化进行实时跟踪，实现生物环境响应性治疗/成像复合功能。

中文关键词： 纳米载体；药物控释；成像增强；结构稳定性；同步调控

英文摘要： The ideal diagnostic & therapeutic systems based on nano-assemblies of block copolymers should satisfy the requirements of high structural stability, stimuli-responsive drug release and enhanced imaging properties. However generally, there are dilemmas between the structural stability and the drug release rate, as well as the enhancement in imaging properties. With the aim of solving these problems, we attempt to synthesize a serious of stimuli-responsive amphiphilic block copolymers, in which the oxidation-reduction or light-sensitive trigger moieties are designed to cage the primary amino groups in the side chains of the hydrophobic blocks. Fluorescence or magnetic resonance imaging moieties that can respond to the change in the surrounding microenvironment are also introduced into the hydrophobic blocks of the copolymers. Based on these amphiphilic block copolymers, nano-assemblies integrated with fluorescence or magnetic resonance imaging property and controlled drug release can be obtained. After being internalized into the tumor cells, the trigger groups can undergo stimuli-responsive dissociation and structural arrangement to decage the primary amino groups, which can induce the subsequent crosslinking between the copolymer chains to stabilize the nano-assemblies. At the same time, due to the protonation of the unreactive primary amino groups, the hydrophobic-hydrophilic transition can occur within the hydrophobic region of these nano-assemblies resulting in effective drug release; and the release process can be tracked in real-time via the change in the fluorescence emission or the MRI contrast. Therefore, multiple functions of biological stimuli-responsive therapy and diagnostic imaging can be fulfilled.

英文关键词： Nano-carriers;Controlled drug release;Enhanced imaging properties;Structural stability;Synchronized regulation