螺旋结构聚多糖改性用作多功能医用载体的研究

For amylose with helicalstructure, its host-gust inclusions and new applications have been important research topics in natural polymeric materials and supramolecular chemistry. In this project, various water-soluble cationic polymers with linear, branched or dendritic structure will be conjugated respectively to amylose backbone by efficient click preparation routes in order to provide amylose with improved water solubility and colloidal stability of its inclusion complexes as well as multifunctional characteristics capable of interacting with DNA or siRNA. For the resultant amylose conjugates, their inclusions with some anti-cancer drugs as such as 5-fluorouracil, doxorubicin and paclitaxel will be investigated mainly by fluorescence spectroscopy and micro-calorimetry, and their complexation with DNA or siRNA will be studied mainly by gel electrophoresis, light scattering and transmission electron microscopy. Moreover, their release behaviors for loaded drugs, gene transfection efficiency and the synergistic mechanism between loaded drug and gene will be also studied in details. It is expected that these new studies can result in novel multifunctional amylose-based carriers for the co-delivery of drug and gene, which will have an important significance to the modification and applications of amylose and other polysaccharids with helical conformations.

具有螺旋结构的直链淀粉，其主-客体分子包合与应用新途径的研究，一直是天然高分子材料及超分子化学研究领域的重要课题。本项目拟首次通过点击合成技术将水溶性线形、支化状、树枝形阳离子聚合物链段分别偶联到直链淀粉分子链上，同时优化有关合成条件及产物结构，以期克服该聚多糖主体分子以往难溶于水、其包合物在水体系中易聚沉等不足，并赋予其易与DNA或siRNA作用的多功能化结构特征；在此基础上，拟采用荧光光谱、微量热等方法研究改性产物与5-氟脲嘧啶、阿霉素、紫衫醇等抗肿瘤药物分子之间的主客体相互作用及包合特性，借助凝胶电泳、光散射及透射电镜等手段研究改性产物与DNA或siRNA之间的分子复合与作用机理，同时探讨有关药物释放行为、基因转染效率及药物与基因协同增效机制，以期构建一类基于天然高分子的、可直接用于药物和基因共传递的多功能载体。本项目工作，对于促进直链淀粉及其它螺旋结构聚多糖的改性研究有重要意义。

具有螺旋结构的直链淀粉，其主-客体分子包合与应用新途径的研究，一直是天然高分子材料及超分子化学研究领域的重要课题。本项目首次通过点击合成技术将水溶性线形、支化状、树枝形阳离子聚合物链段分别偶联到直链淀粉分子链上，同时优化有关合成条件及产物结构，以期克服该聚多糖主体分子以往难溶于水、其包合物在水体系中易聚沉等不足，并赋予其易与DNA或siRNA作用的多功能化结构特征；在此基础上，采用荧光光谱、微量热等方法研究改性产物与5-氟脲嘧啶、阿霉素、紫衫醇等抗肿瘤药物分子之间的主客体相互作用及包合特性，借助凝胶电泳、光散射及透射电镜等手段研究改性产物与DNA或siRNA之间的分子复合与作用机理，同时探讨有关药物释放行为、基因转染效率及药物与基因协同增效机制，以期构建一类基于天然高分子的、可直接用于药物和基因共传递的多功能载体。本项目工作，对于促进直链淀粉及其它螺旋结构聚多糖的改性研究有重要意义。基于本项目研究，已在国外学术刊物上发表SCI 论文22 篇，授权中国发明专利3 项；此外，还培养博士后1 名、博士生5 名和硕士生2名。

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