Synthesis and Investigation of New Core-Shell Nanoparticles as Molecular Carrier Systems

这项联合计划的目标是开发高效合成新的树枝状核壳纳米载体，并系统地研究分子结构对其在水体系中包裹和传输疏水分子的影响。通过结合关组(美国加州大学欧文分校)一锅法合成具有可控拓扑结构的疏水性聚烯烃核心的专业知识和HAAG小组(德国柏林Freie University sitaet)高效合成亲水性和生物相容性聚甘油壳的专业知识，拟议的研究旨在开发合成核壳纳米载体的有效方法，并揭示所产生的新的两亲性分子结构的基本结构-性质信息。在拟议的联合研究中，首先，关团队将使用他们之前获得的NSF职业资助开发的链步聚合方法，合成一系列具有从线形、超支化到树枝状结构的疏水聚烯烃核心。在链式催化剂的作用下，一锅聚合得到了具有核-壳结构的树枝状纳米粒子。聚合物的合成效率、通用性以及独特的结构和性能使这一策略令人兴奋，值得进一步研究。这些核心将携带不同的官能团，如内部的芳香单元和表面的伯羟基或炔基。随后，HAAG小组将使用他们建立的方法，将生物相容性和亲水性树枝状聚甘油壳从/到亲水性聚烯烃核。最后，通过UV/Vis和荧光光谱研究了所合成的核壳纳米载体对具有代表性的疏水分子在水溶液中的包覆和分子传输性能。这些核壳纳米载体的基本溶液性质和它们的聚集行为也将通过光散射和低温电子显微镜进行仔细的研究。通过这项研究获得的结构-性质关系的理解将为设计高效的分子纳米载体提供关键的见解，这些分子纳米载体可能会在墨水配方和药物输送方面找到潜在的应用。这项拟议活动的智力价值有两个方面：(1)两种独特和互补的新合成方法之间的真正结合将导致开发获得新型核-壳纳米载体的高效合成路线；(2)通过系统地改变核-壳结构的结构和研究其溶液和分子传输性质，将在如何设计适用于广泛应用的高效分子纳米载体方面获得重要的见解。这项联合研究的广泛影响是多方面和重大的：(1)对行业的影响：高效分子纳米载体简易合成的成功开发将对包括医疗保健、药物配制和输送、油墨和涂料配方在内的各种行业产生巨大影响。(2)对纳米科学的影响：制造生物相容、复杂和多功能软纳米材料的有效方法将加速许多纳米技术的发展，包括纳米医学和医疗诊断。(3)教育影响：拟议的跨学科和国际合作研究活动将为学生提供许多领域的优秀培训，包括有机合成、有机金属、聚合物合成和物理性质研究，以及纳米科学。这将为培养研究生和本科生提供很好的机会，特别是对少数民族和女性学生。两个小组之间的频繁交流不仅将使学生接触到不同的专业知识和技术，还将为他们提供在科学合作方面获得国际经验的机会。

The objective of this joint proposal is to develop highly efficient syntheses for new dendritic coreshell nanocarriers and to systematically investigate the effects of molecular architecture on their encapsulation and transport of hydrophobic molecules in aqueous systems. By combining the expertise of the Guan group (UC Irvine, USA) for one-pot synthesis of hydrophobic polyolefin cores with controllable topologies and the Haag group (Freie Universitaet Berlin, Germany) for efficient synthesis of hydrophilic and biocompatible polyglycerol shells, the proposed study is aimed to develop efficient methodology for the synthesis of core-shell nanocarriers and to reveal basic structure-property information on the resulting new amphphilic molecular architectures. In the proposed joint studies, first, the Guan group will synthesize a series of hydrophobic polyolefin cores with architectures ranging from linear, hyperbranched, to dendritic by using their chain walking polymerization methodology developed with their prior NSF CAREER grant. Using a chain walking catalyst, dendritic nanoparticles including core-shell nanostructures have been obtained in one-pot polymerization. The synthetic efficiency, versatility, combined with the unique structure and properties for the polymers make this strategy exciting for further investigation. These cores will carry different functional groups such as aromatic units in the interior and primary hydroxyl or alkyne groups on the surface. Subsequently, the Haag group will graft biocompatible and hydrophilic dendritic polyglycerol shells from/to the hydrophic polyolefin cores by using their established methodologies. Finally, the encapsulation and molecular transport properties of the synthesized core-shell nanocarriers for representative hydrophobic molecules in aqueous solution will be investigated by UV/Vis and fluorescence spectroscopy. The basic solution properties of these core-shell nanocarriers and their aggregation behavior will also be carefully examined by light scattering and cryo- TEM. The understanding of structure-property relationships gained from this study will provide critical insight for designing highly efficient molecular nanocarriers that may find potential applications for ink formulation and drug delivery. The intellectual merit of this proposed activity is 2-fold: (1) the true marriage between two unique and complementary new synthetic methodologies shall lead to the development of highly efficient synthetic routes for accessing novel core-shell nanocarriers; (2) through systematically varying the architecture/structure of the core-shell constructs and investigating their solution and molecular transport properties, important insights will be gained on how to design efficient molecular nanocarriers for a broad range of applications. The broad impacts of this joint study is numerous and significant: (1) Impact to the industry: successful development of facile synthesis of efficient molecular nanocarriers shall have enormous impacts on various industries including health care, drug formulation and delivery, ink and paint formulations. (2) Impact to nanoscience: efficient methods for making biocompatible, complex and multifunctional soft nanomaterials shall accelerate many nanotechnology developments including nanomedicine and medical diagnostics. (3) Educational impacts: The proposed multi-disciplinary and international collaborative research activity will provide excellent training for students in many areas including organic synthesis, organometallic, polymer synthesis and physical property studies, and nanoscience. This will provide great opportunities to train graduate and undergraduate students, especially for minority and women students. The frequent exchanges between the two groups will not only expose the students to different expertise and techniques, but provides them opportunities to gain international experience in scientific collaborations.