可生物响应性调控的磁共振成像/药物输运复合功能核交联胶束纳米载体研究

项目名称： 可生物响应性调控的磁共振成像/药物输运复合功能核交联胶束纳米载体研究

项目编号： No.51273190

项目类型： 面上项目

立项/批准年度： 2013

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： 80万元

中文摘要： 针对基于高分子胶束组装体的T1型磁共振成像(MRI)造影剂存在的结构稳定性差、不能有效实现MRI信号的响应性增强以及作为药物载体时负载效率低和不可控释放等局限性，本项目拟合成一系列以结构稳定的嵌段共聚物核交联胶束为载体的生物响应性磁共振造影剂，并兼具可调控荧光成像和响应性释放共价键合药物的复合功能。利用pH响应性交联内核在弱酸性环境下发生疏水-亲水转变调控钆络合物造影基元所处的微环境，实现MRI信号的响应性增强；进一步在交联内核中引入NBD荧光基元，力图实现MRI/荧光双模成像的pH值响应性调控；还将融合MRI信号的响应性调控与新型药物负载/控释策略，采用含二硫键的交联剂进行核交联并在核内共价键接具有巯基响应性触发释放特性的抗肿瘤前药基元，合成巯基敏感的具有MRI造影增强/药物输运复合功能的诊疗体系。该项目的实施预期将为新型大分子造影剂和诊疗体系的设计和优化提供重要依据。

中文关键词： 高分子纳米医药；结构稳定性；交联；荧光成像；核磁共振成像

英文摘要： In order to overcome major limitations of polymeric assemblies- based T1-type magnetic resonance imaging (MRI) contrast agents, such as weak structural stability, inefficiency in bioreponsive enhancement of MR imaging contrast, and low drug loading efficiency and uncontrollable drug realease when acting as drug delivery nanocarriers, in this application, we attempt to synthesize a series of bioresponsive macromolecular MRI contrast agents integreted with multiple functions of stimuli-tunable fluorescence emission and stimuli-triggered release of covalently conjugated drugs based on structurally stable core- crosslinked (CCL) micelles of diblock copolymers. The bioresponsive enhancement of MR imaging contrast can be attained by tunable changes in the surrounding microenvironment of DOTA(Gd) moieties induced by hydrophobic-hydrophilic transition of the pH-sensitive crosslinked core under mildly acidic conditions. We will then covalently conjugate NBD fluorescent moieties into the crosslinked core aiming to achieve pH-enhanced magnetic resonance and fluorescence dual-modality imaging. Furthermore, by combining bioresponsive magnetic resonance imaging with drug delivery and regulated drug release, thiol-sensitive functional nanomedicine system based on CCL micelles with integreted functions of MR imaging and drug d

英文关键词： polymeric nanomedicine；structural stability；crosslinking；fluorescent imaging；magnetic resonance imaging