基于开环反应构建具有靶向、成像和载药功能的新型PGMA衍生物基因载体及其性能研究

The construction of multifunctional polycation gene vector has become a hot research topic in biomaterial areas. The aminated poly(glycidyl methacrylate)s can be constructed for multifunctional gene vectors with high efficiency and compromised toxicity. In this project, a series of novel multi-hydroxyl PGMA-based gene vectors with unique properties of cell-targeting, bio-imaging and drug-loading will be synthesized by the ring-opening addition reaction with various different functions of amino compounds (galactose, tetraphenylethylene/spiropyran and ethanol amine). The effects of transfection efficiency, cell toxicity, drug-loading and synergistic therapy will be studied. The bio-imaging capability of PGMA-based gene vectors in cells and the relationship between the fluorescence intensity and drug release will be evaluated. This project will open new avenues for the fabrication of gene delivery systems with high performances. A series of novel PGMA-based non-virus gene vectors with unique properties of cell-targeting, bio-imaging and drug-loading may therefore offer new opportunities in the area of gene therapy.

多功能化阳离子聚合物基因载体是生物材料领域的未来发展方向。近期研究表明，胺化的聚甲基丙烯酸缩水甘油酯（PGMA）可有效用于构建低毒高效阳离子基因载体。本项目拟通过利用PGMA聚合物与不同种类胺基化合物（包括胺基半乳糖、胺基四苯基乙烯／螺吡喃和乙醇胺）进行开环反应，形成功能化阳离子聚合物。该系列聚合物在保持较高的胺基和羟基密度的同时，引入具有靶向功能的分子和具有成像功能的荧光分子，以实现基因载体的多功能化。进一步利用引入荧光基团疏水性实现药物运输的功能，通过研究基因／药物释放与荧光的关系，最终构建出具有靶向、成像、载药功能的高性能PGMA衍生物基因载体。本项目有望为构建多功能新型基因载体提供新思路。

多功能化阳离子聚合物基因载体是生物材料领域的未来发展方向。近期研究表明，胺化的聚甲基丙烯酸缩水甘油酯（PGMA）可有效用于构建低毒高效阳离子基因载体。本项目拟通过利用PGMA聚合物与不同种类胺基化合物（包括胺基四苯基乙烯、胺基酞菁锌、碘海醇碘代物和乙醇胺）进行开环反应，形成功能化阳离子聚合物。该系列聚合物在保持较高的胺基和羟基密度的同时，引入具有成像功能的功能分子和光动力治疗分子，以实现基因载体的多功能化。最终构建出具有成像、多模式治疗功能的高性能PGMA衍生物基因载体。本项目有望为构建多功能新型基因载体提供新思路。