Cationic star polymers: preparation and applications

水溶性阳离子聚合物在造纸中被广泛用作絮凝剂，目前正被认为是DNA输送的载体。基因疗法或基于DNA的药物(包括将合成的DNA分子引入细胞以取代有缺陷的基因)在治疗癌症、艾滋病和神经疾病等各种疾病方面非常有希望，因为它们可以选择性地识别靶点和途径。开发基于DNA的药物的一个重大挑战是缺乏安全和有效的核酸输送系统。这项拟议的研究将通过开发一系列具有理想结构的阳离子星形聚合物来应对这一挑战，作为DNA传递的非病毒载体。这些合成将基于我们之前成功地制备了一种基于环糊精的活性自由基聚合引发剂，该引发剂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型和生物聚合物类型。各种量身定制的改性聚合物将使我们能够确定最大限度地提高DNA传递效率的最佳结构。进一步延长聚合过程中的臂长度可产生新型星形聚合物，可用作造纸的絮凝剂(或助留剂)--阳离子星形聚合物的另一个重要应用。阳离子星形聚合物在分子量与线型聚合物相近的情况下具有更低的溶液粘度，有助于造纸中的羽化过程和改善助留性能。球面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助留机理。几种最先进的技术，特别是皮科力原子力显微镜(AFM)，将被用来可视化聚合物/DNA复合体，并量化DNA复合体形成和填充絮体形成的驱动力(或成键)，提供以前无法实现的信息。从拟议的研究中获得的发现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.