Designing well-defined macromolecule based nanostructures for multi-tasking

该研究项目旨在开发能够协同高效地执行多种预定功能的智能纳米材料。在解决催化、环境传感和生物学等领域的关键问题时，最近确定的主要挑战之一是合成下一代纳米颗粒，这些纳米颗粒将重要功能整合到一个单一系统中。我们的重点是简化这种复杂纳米载体的设计，并开发一种强大的合成方法，以产生能够同时诊断，靶向和治疗的定义明确的分子。为此，我们将使用定制的构建模块和高效化学来构建基于树状大分子和mitoarm聚合物的多功能纳米结构。这些大分子提供了两个独特的平台，完全通过共轭或共价连接和包封的组合引入所需的功能。我们在未来五年内的目标是开发一种可重复的合成路线，策略性地设计跟踪单元的位置（在纳米颗粒的核心或外围），并通过治疗，靶向和增溶剂的确定组合来控制纳米颗粒的整体组成。为了提高对氢诱导极化的效果，我们将开发一种过渡金属基催化剂，将这种成像功能整合到水介质中纳米颗粒的外围。我们将对纳米制剂中不同功能单元的协同作用模式进行详细评估。这项重要研究的结果将指导我们设计和合成具有双模式成像能力的纳米探针。我们的目标是将核心染料的荧光与i)包裹在胶束中或在树状大分子中共价连接的另一种染料结合起来，用于荧光共振能量转移过程，以及ii)与树状大分子外围的对氢诱导极化结合起来。

This research program is directed at developing smart nanomaterials which can perform multiple pre-determined functions cooperatively and efficiently. One of the major challenges in addressing key issues in areas including catalysis, environmental sensing and biology, was recently identified to be the synthesis of next generation nanoparticles which consolidate important functions into a single system. Our focus is to simplify the design of such complex nanocarriers, and to develop a robust synthetic methodology that yields well-defined molecules capable of, for example, simultaneous diagnosis, targeting and therapy. For this purpose, we will construct dendrimers and miktoarm polymer based multifunctional nanostructures using tailor-made building blocks and highly efficient chemistry. These macromolecules offer two unique platforms for introducing desired functions entirely by conjugation or a combination of covalent linking and encapsulation. Our goals within the next five years are to develop a reproducible synthetic route to strategically engineer the location of tracking units (in the nanoparticle core or at the periphery), and in controlling the overall composition of the nanoparticle with a defined combination of therapeutic, targeting and solubilizing agents. To enhance the efficacy of parahydrogen induced polarization, we will develop a transition metal-based catalyst for incorporating this imaging functionality at the periphery of nanoparticles in an aqueous medium. We will carry out a detailed evaluation of the cooperative mode of action of different functional units in a nanoformulation. The results from this essential study will guide us in the design and synthesis of nanoprobes capable of dual mode imaging. We aim to combine fluorescence from the dye at the core with i) another dye encapsulated in micelles or covalently linked in dendrimers for fluorescence resonance energy transfer processes, and ii) with parahydrogen induced polarization at the periphery of dendrimers.