树枝状聚缩酮的合成、自组装及应用

项目名称： 树枝状聚缩酮的合成、自组装及应用

项目编号： No.21474115

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 吴德成

作者单位： 中国科学院化学研究所

项目金额： 94万元

中文摘要： 树枝状聚合物是一种结构完全规整和高度支化的高分子材料，在生物医学领域受到了日益广泛的关注。已开发的树枝状聚合物多数是不可降解的，可降解的树枝状聚合物大多为水解型聚酯类材料，远不能满足生物医学应用的需求，如生物选择性降解的需要。本项目的研究目标是开发一类新型酸降解的树枝状聚缩酮及其两亲性共聚物，研究自组装和解组装行为，并探索其在生物医学领域如药物和基因输送上的应用。具体研究手段是设计和合成具有高度非等活性的双缩酮单体，采用高效温和的点击加成手段制备树枝状聚缩酮，进一步改性或耦合得到一系列两亲性树枝状共聚物，研究共聚物溶液组装行为构筑多种形貌的组装体，通过体外细胞实验和裸鼠移植瘤的治疗效果评价实验，评估新型树枝状聚缩酮、共聚物及组装体在药物和基因输送上的应用前景。预计相关研究成果将为开发基于新型树枝状聚缩酮的生物医用高分子材料奠定良好的基础。

中文关键词： 树枝状聚缩酮；点击合成方法；自组装；药物载体；基因载体

英文摘要： Dendrimers are a class of artificial macromolecules with a highly branched three-dimensional architecture and well-defined chemical structure. Since their development in the mid-80s, dendrimers have been prominent synthetic macromolecules in the field of biomedical science. Due to the unique ability to control size, structural properties, and polydispersity, dendrimers have achieved significant success in a variety of biomedical applications. While the use of dendrimers in the clinic has still not reached the success of linear polymers, this fact is attributed to the relative newness of this field and the difficulties encountered with the development of novel species with on-demand property at a larger scale. For example, most of the developed dendrimers are not degradable, and most of the degradable dendrimers are polyester-based dendrimers with hydrolytic degradation. pH-responsive degradation is an important property for biomedical applications, but there is not this kind of dendrimers developed by now. In this proposal, we will develop a novel class of pH-degradable polyketal dendrimers and their amphiphilic derivatives, investigate self-assembly and de-assembly behaviors of amphiphilic dendrimers, and explore their potential biomedical applications in drug and gene delivery. The detailed approaches are 1) to design and synthesize ketal-containing monomers with highly non-equal reactivity; 2) to adopt simple and efficient 'click' methodologies for production of novel acid-degradable dendrimers; 3) to yield amphiphilic dendrimers through further modification and coupling of dendrons; 4) to obtain several kinds of assemblies like micelles, vesicles and tubes via controlled self-assembly of the amphiphilic dendrimers; and 5) evaluate their potential applications as smart drug and gene vectors. We expect the results obtained from this project will greatly guide the further exploration of this novel polyketal dendrimers towards the successful use in the clinic for practical biomedical applications.

英文关键词： polyketal dendrimers;click methodology;self-assembly;drug carriers;gene vectors