Copolymer Nanostructures Containing Polyelectrolyte Blocks and their Complexes with Molecules of Complementary Charge

技术概述：本研究将采用多相嵌段共聚物组装的原理来描绘定义一系列新的嵌段共聚双膦酸酯-小分子纳米结构的结构、稳定性和释放特性的参数空间。众所周知，膦酸酯基团与无数基质强烈络合，所述基质包括金属、金属氧化物、羟基磷灰石（骨）、牙釉质和阳离子药物。因此，将合成含有具有膦酸铵侧基的嵌段的多相共聚物，重点是控制嵌段分子量和结构，并且它们将与具有互补电荷的低分子量货物分子络合以形成纳米结构。 研究将侧重于开发它们的化学成分，块结构，纳米结构的大小，形状，电荷，胶体稳定性和释放特性之间的关系。所获得的知识将影响我们对静电络合和聚合物形态相对于形成和释放各种聚合物药物递送复合物的作用的理解。学生将有机会在聚合物科学和生物科学的接口进行研究。他们的工作将被整合到VA Tech关键技术和应用科学研究所的多元化，更广泛的纳米科学团队中。自20世纪70年代以来，制药科学和分子生物学的巨大进步现在提供了无数具有治疗疾病和纠正遗传缺陷潜力的治疗分子。实现这些分子的益处的关键挑战在于它们安全有效地递送到适当的组织和细胞。软材料分子工程的进展代表了实现迄今为止所取得的进展和投资的领先解决方案。该项目介绍了一系列含有强络合聚膦酸盐阴离子的嵌段共聚物，这些阴离子可以转化为具有封装、保护、然后释放具有互补阳离子电荷的各种药物的潜力的纳米结构。学生将学习设计和合成嵌段共聚物和制备纳米结构，他们将在更广泛的团队中工作，以更好地了解他们的新材料的特性，可以造福社会。该项目包括大力招募和维持各级各类学生。

TECHNICAL SUMMARY:This research will employ principles of multiphase block copolymer assembly to delineate the parameter space that defines the structures, stabilities and release properties of a family of new block copolybisphosphonate-small molecule nanostructures. Phosphonate groups are well-known to complex strongly to a myriad of substrates including metals, metal oxides, hydroxyapatite (bone), tooth enamel, and cationic drugs. Thus, multiphase copolymers containing blocks with ammonium phosphonate pendant groups will be synthesized with an emphasis on controlled block molecular weights and architectures and they will be complexed with low molecular weight cargo molecules with complementary charges to form nanostructures. Research will focus on developing relationships among their chemical compositions, block architectures, nanostructure sizes, shapes, charge, colloidal stabilities and release characteristics. The knowledge gained will impact our understanding of the roles of electrostatic complexation and polymer morphology relative to formation and release of a wide variety of polymeric drug delivery complexes. Students will have the opportunity to conduct research at the interface of polymer science and biological sciences. Their work will be integrated into the diverse, broader nanoscience team in the Institute for Critical Technologies and Applied Sciences at VA Tech. NON-TECHNICAL SUMMARY:Dramatic progress in pharmaceutical sciences and molecular biology since the 1970s now provides a myriad of therapeutic molecules with potential for treating diseases and correcting genetic defects. The key challenge to realize the benefits of these molecules lies in their safe and effective delivery to the appropriate tissue and cell. Advances in the molecular engineering of soft materials represent a leading solution to realize the progress and investments heretofore made. This project introduces a family of block copolymers containing strongly-complexing polyphosphonate anions that can be transformed into nanostructures with potential for encapsulating, protecting, then releasing a wide variety of drugs that have complementary cationic charge. Students will learn to design and synthesize block copolymers and prepare nanostructures, and they will work within a broader team to better understand the properties of their new materials that can benefit society. The project incorporates an intense effort to recruit and sustain a diverse group of students at all levels.