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

该联合提案的目的是开发新的树枝状核壳纳米载体的高效合成，并系统地研究分子结构对其在水性体系中包封和转运疏水分子的影响。通过结合关氏集团的专业知识，（UC Irvine，USA），用于一锅法合成具有可控拓扑结构和Haag基团的疏水性聚烯烃核（Freie Universitaet柏林，德国）用于有效合成亲水性和生物相容性聚甘油壳，该研究旨在开发用于合成核-壳纳米载体的有效方法，并揭示基本结构-所得新的两亲性分子结构的性质信息。在拟议的联合研究中，首先，Guan小组将通过使用他们先前的NSF CAREER资助开发的链行走聚合方法，合成一系列具有线性，超支化和树枝状结构的疏水聚烯烃核。使用链行走催化剂，在一锅聚合中获得了包含核壳纳米结构的树枝状纳米颗粒。合成效率，多功能性，结合独特的结构和性能的聚合物，使这一战略令人兴奋的进一步研究。这些核将携带不同的官能团，例如内部的芳族单元和表面上的伯羟基或炔基。随后，Haag小组将通过使用其已建立的方法，将生物相容性和亲水性树枝状聚甘油壳从亲水性聚烯烃核移植到亲水性聚烯烃核。最后，通过紫外/维斯和荧光光谱研究了合成的核壳纳米载体在水溶液中对代表性疏水分子的包封和分子传输性能。这些核-壳纳米载体的基本溶液性质及其聚集行为也将通过光散射和cryo-TEM仔细检查。从这项研究中获得的结构-性质关系的理解将提供关键的洞察力，设计高效的分子纳米载体，可能会发现潜在的应用墨水配方和药物输送。该拟议活动的智力价值是2-倍：（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用于获得新型核-壳纳米载体的高效合成路线;（2）通过系统地改变核-壳构建体的架构/结构并研究它们的溶液和分子传输性质，将获得关于如何设计用于广泛应用的有效分子纳米载体的重要见解。这项联合研究的广泛影响是众多的和重要的：（1）对行业的影响：成功开发高效分子纳米载体的简易合成将对包括医疗保健，药物配制和递送，油墨和涂料配方在内的各个行业产生巨大影响。(2)对纳米科学的影响：制备生物相容的、复杂的和多功能的软纳米材料的有效方法将加速许多纳米技术的发展，包括纳米医学和医学诊断。(3)教育影响：拟议的多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，特别是少数民族学生和女生提供巨大的机会。两个小组之间的频繁交流不仅使学生接触到不同的专业知识和技术，而且为他们提供了在科学合作中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.