Cationic star polymers: preparation and applications

水溶性阳离子聚合物已被广泛用作造纸中的絮凝剂，并且这些聚合物现在被认为是DNA递送的载体。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缺陷基因）由于其对靶点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具前景。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递送系统。拟议的研究将通过开发一系列具有理想结构的阳离子星星聚合物作为DNA递送的非病毒载体来应对这一挑战。该合成将基于我们先前在制备用于活性自由基聚合的环糊精基引发剂方面的成功，该引发剂允许制备具有可控臂结构、电荷类型和电荷分布的21-臂星星聚合物。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递送效率。进一步延长聚合中的臂链长度产生新型星星聚合物，其可用作造纸的絮凝剂（或助留剂）-阳离子星星聚合物的另一重要应用。阳离子星星型聚合物在分子量接近线性聚合物时，溶液粘度低得多，有利于制浆过程，改善造纸留着性能。球形尺寸可控的星星聚合物使我们能够从胶体科学的角度揭示其助留机理。几个国家的最先进的技术，特别是皮力原子力显微镜（AFM），将被用来可视化的聚合物/DNA复合物，并量化的驱动（或结合）的DNA复合物的形成和填料絮凝物形成的力量，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制药，造纸和水产养殖业和加拿大公共卫生。

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.