Structure and Dynamics of Block Ionomer Complexes

该项目的主要目标是探索两种分散的复合纳米材料，统称为嵌段离聚物或BIC。第一种材料是由含有离子段和水溶性非离子段的双亲水嵌段共聚物与带相反电荷的多离子反应合成的。这些材料在水介质中形成胶束状的聚集体，具有多离子复合物核和亲水的非离子电晕。第二种材料是由含有离子段和不溶于水的非离子段的嵌段共聚物的胶束与带相反电荷的多离子反应得到的。这种材料含有具有疏水核心的胶束，如成核粒子，被不溶性多离子络合物层包围，以及由过量存在的多离子产生的带电亲水电晕。BIC领域是十多年前在选择性溶剂中聚电解质络合物和离子嵌段共聚物自组装研究的交叉而产生的。已经确定了几种有前途的BIC材料的应用，包括DNA，治疗蛋白，低分子质量药物和显像剂的递送。常规聚电解质配合物的一个基本性质是能够与溶液中的其他聚电解质组分进行高度协同的多离子交换反应。初步研究表明，这种涉及BIC的反应也可以进行。虽然这些反应对BIC的自组装和实际应用具有重要意义，但尚未进行系统的研究。本提案将利用荧光技术来解决这一缺陷，以确定这些反应的速率和方向，并了解BIC的核壳结构对其动态性质的贡献。新材料将被合成和表征，如BIC是由具有交联离子核的聚电解质胶束和具有疏水核和多离子电晕的非离子水溶性电晕胶束与各种多离子（包括dna和蛋白质）反应得到的。BIC的稳定性、尺寸、电荷和形貌将采用物理化学方法相结合的方法来确定。特别是，该提案将采用原子力显微镜来确定颗粒的形貌和小角中子散射来确定颗粒的内部结构。BIC的理论分析将与莫斯科国立大学的科学家合作进行。总体而言，该提案将极大地促进对BIC的实验和理论理解，并开发可用于生物医学应用的新型BIC材料。该提案将通过为材料和生物医学科学家之间的合作创造有利的环境而产生更广泛的影响，并将有助于内布拉斯加大学和其他大学的学生和科学家的跨学科培训。研究结果将通过药物传递和纳米医学中心的科学会议和研讨会传播，这将推动聚合物纳米材料在药物和基因传递中的应用。研究和教育的整合将受益于PI和Co-PI教授的聚合疗法课程，该课程结合了最近的科学发现。积极利用互联网，例如在网上发布课程和讲座，以加强传播。内布拉斯加州的科学和技术理解将通过向小型医学院等广泛的社区团体作报告而得到加强。这些协同活动将展示科学发现与社会效益之间的联系，提供聚合物材料应用的例子，包括本项目预期的新发现。

The major goal of this project is to explore two types of dispersed composite nanomaterialscollectively called the block ionomers complexes or BIC. The first materials are synthesized byreacting dual hydrophilic block copolymers, containing ionic and water soluble nonionicsegments, with oppositely charged polyions. Such materials form micelle-like aggregates withthe polyion complex core and hydrophilic nonionic corona in aqueous media. The secondmaterials are obtained by reacting micelles from block copolymers, containing ionic and waterinsoluble nonionic segments with the polyions of opposite charge. Such materials contain themicelles with hydrophobic cores as nucleating particles surrounded by insoluble polyioncomplex layer and a charged hydrophilic corona from the polyion present in excess. The area of BIC has emerged a decade ago as a result of intersection of the studies on the selfassemblyof polyelectrolyte complexes and ionic block copolymers in selective solvents. Severalpromising applications of BIC materials have been determined, including the delivery of DNA,therapeutic proteins, low molecular mass drugs and imaging agents. One fundamental propertyof regular polyelectrolyte complexes is the ability to participate in highly cooperative polyioninterchange reactions with other polyelectrolyte components present in solution. Initial studiessuggest that such reactions involving BIC can also proceed. Although these reactions are of greatimportance for the self-assembly and practical use of BIC no systematic studies in this area havebeen conducted. This proposal will address this deficiency using fluorescence technique todetermine rates and directions of these reactions and understand the contribution of the core-shellarchitecture of BIC to their dynamic properties. Novel materials will be synthesized and characterized, such as BIC obtained by reactingpolyelectrolyte micelles having cross-linked ionic cores and nonionic water soluble corona ormicelles having hydrophobic cores and polyion corona with various polyions, including DNAand proteins. The stability, size, charge and morphology of the BIC will be determined using acombination of physicochemical methods. In particular, the proposal will employ forcharacterization of BIC the Atomic Force Microscopy to determine the particle topography andSmall Angle Neutron Scattering to determine the particle internal structure. A theoreticalanalysis of the BIC will be carried out in collaboration with scientists at Moscow StateUniversity. Overall the proposal will greatly advance experimental and theoretical understandingof BIC and develop new classes of BIC materials that can be useful in biomedical applications. The proposal will have broader impact by creating a favorable environment for collaborationbetween the material and biomedical scientists and will contribute to interdisciplinary training ofstudents and scientists in the University of Nebraska and beyond. The results of the studies willbe disseminated through scientific meetings and seminars within the Center for Drug Deliveryand Nanomedicine, which will advance applications of polymer nanomaterials in drug and genedelivery. The integration of research and education will benefit from the course on PolymerTherapeutics taught by the PI and Co-PI, which incorporates recent scientific findings. Thedissemination will be enhanced by the active use of Internet, such as online posting of the courseand lectures. The scientific and technological understanding in the State of Nebraska will beenhanced by presentations to broad community groups such as MiniMedical School. Thesesynergistic activities will demonstrate linkage between scientific discoveries and societal benefitby providing the examples of application of polymer materials including the new findingsanticipated from this project.