Cationic star polymers: preparation and applications

水溶性阳离子聚合物在造纸中广泛用作絮凝剂，这些聚合物现在被认为是DNA传递的载体。基因疗法或基于DNA的药物（涉及将合成DNA分子引入细胞以取代有缺陷的基因）由于其对目标和途径的选择性识别，在治疗癌症、艾滋病和神经系统疾病等各种疾病方面极有希望。开发基于dna的药物的一个重大挑战是缺乏安全有效的核酸输送系统。提出的研究将通过开发一系列具有理想结构的阳离子星型聚合物作为DNA传递的非病毒载体来解决这一挑战。该合成将基于我们之前成功制备的环糊精引发剂，用于活性自由基聚合，可以制备具有可控臂结构，电荷类型和电荷分布的21臂星形聚合物。阳离子聚合物的制备也将扩展到线性和生物聚合物类型。各种定制修饰的聚合物将使我们能够确定最佳结构，以最大限度地提高DNA传递效率。在聚合过程中进一步延长臂链长度可以产生新的星型聚合物，这种聚合物可以用作造纸的絮凝剂（或助留剂）——这是阳离子星型聚合物的另一个重要应用。阳离子星型聚合物在分子量与线性聚合物相似的情况下，溶液粘度低得多，有利于造纸过程的简化，提高了造纸中的保留性能。球状尺寸可控的星形聚合物使我们能够从胶体科学的角度揭示其保留机理。几种最先进的技术，特别是微力原子力显微镜（AFM），将被用于可视化聚合物/DNA复合物，并量化DNA复合物形成和填料絮团形成的驱动（或键合）力，提供以前无法实现的信息。从拟议的研究中获得的结果将大大有利于加拿大的制药、造纸和水产养殖业以及加拿大的公共卫生。

Water-soluble cationic polymers have been extensively used as flocculants in papermaking and these polymers are now being considered as vehicles for DNA delivery. Gene therapy or DNA-based drugs (involving the introduction of synthetic DNA molecules to a cell to replace defective genes) are extremely promising for dealing with various diseases such as cancer, AIDS and neurological disorders due to their selective recognition of targets and pathways. A significant challenge in exploiting DNA-based drugs is the lack of a safe and efficient delivery system for nucleic acids. The proposed research will address this challenge by developing a range of cationic star polymers with desirable structures as non-viral vectors for DNA delivery. The syntheses will be based on our previous success in preparing a cyclodextrin-based initiator for living free-radical polymerization that permits the preparation of 21-arm star polymers with controllable arm structure, charge types and charge distribution. The preparation of cationic polymer will also be extended to linear and biopolymer types. The variety of tailor-modified polymers will enable us to identify the optimal structures for maximizing the DNA delivery efficiency. Further extending the arm chain lengths in polymeri- zation generates novel star polymers that can be used as flocculants (or retention aids) for papermaking - another important application of cationic star polymers. With much lower solution viscosity at the molecular weights similar to linear ones, cationic star polymers will facilitate the making-down process and improve retention performance in papermaking. The star polymers with controllable spherical sizes enable us to reveal the retention mechanism from a colloid scientific point of view. Several state-of-art techniques, a Pico-force atomic force microscope (AFM) in particular, will be utilized to visualize the polymer/DNA complex and to quantify the driving (or bonding) forces for both DNA complex formation and filler floc formation, providing information unachievable previously. The findings obtained from the proposed research will significantly benefit Canadian pharmaceutical, papermaking, and aquaculture industries and Canadian public health.