Designing well-defined macromolecule based nanostructures for multi-tasking

这项研究计划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。最近发现，解决催化、环境传感和生物学等领域的关键问题的主要挑战之一是合成下一代纳米颗粒，它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，产生定义明确的分子，例如，能够同时诊断、靶向和治疗。为此，我们将使用定制的积木和高效的化学手段来构建树枝状大分子和混合臂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，用于完全通过共轭或共价连接和封装的组合来引入所需的功能。我们在未来五年的目标是开发一种可重复使用的合成路线，以战略性地设计跟踪单元的位置(在纳米颗粒核心或外围)，并通过确定的治疗剂、靶向和增溶剂的组合来控制纳米颗粒的总体组成。为了提高仲氢诱导极化的效率，我们将开发一种基于过渡金属的催化剂，用于在水介质中纳米颗粒的外围结合这种成像功能。我们将对纳米配方中不同功能单元的协同作用模式进行详细的评估。这项重要研究的结果将指导我们设计和合成能够双模成像的纳米探针。我们的目标是将来自核心的染料的荧光与i)包裹在胶束中或共价连接在树枝状大分子中的另一种染料结合在一起，以进行荧光共振能量转移过程，以及ii)在树枝状大分子的外围使用对氢激发极化。

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.