Engineering Block Copolymer and Hybrid Nanotechnologies of Well-Defined Architecture

可以合成由疏水性和亲水性重复单元的单独嵌段组成的两亲性二嵌段共聚物（例如AAAAAABBBBBB），使得它们在特定条件下自组装以形成纳米级的明确形状和尺寸的聚集体。目前，人们对生产稳定的纳米技术有相当大的兴趣，这些技术可用于制药和生物医学行业的广泛应用。在这一点上，在这些工业中，很大程度上只有球形嵌段共聚物聚集体已经向前发展到商业开发。例如，在制药工业中，许多依赖于在球形嵌段共聚物胶束中配制的抗癌药物已经进入临床开发。然而，除了球形形状之外，两亲性共聚物可以被工程化以形成具有简单、复杂和/或分级形状的聚集体。重要的是，共聚物聚集体的形状对它们的性能具有深远的影响，例如疏水性和亲水性货物的负载能力，货物的保留和在各种介质中的运输性能。迄今为止，只有少数已建立的生物相容性共聚物（例如聚乙二醇-嵌段-聚己内酯（PEG-b-PCL）、PEG-b-聚（D，L-丙交酯）（PEG-b-PLA））已显示在水溶液中可靠地形成非球形形状，例如蠕虫状丝状胶束和囊泡。因此，人们对设计新的生物相容性共聚物感兴趣，这些共聚物能够在水溶液中可再现地产生不同的形态。除了疏水和亲水分子的包封之外，这些两亲性嵌段共聚物还可用于将无机金属纳米颗粒（如金纳米颗粒（AuNP））组织成明确定义的3D结构。这些聚合物/金属混合纳米结构具有独特的性质和功能，单独使用金属纳米颗粒无法实现，并且在生物医学应用中具有显着的潜力，例如成像，光热治疗，放射治疗和生物传感器。因此，该NSERC提案要求提供资金，以支持设计和开发新的两亲性生物相容性材料的基础研究，这些材料能够生产具有确定形状和尺寸的共聚物和药物或共聚物和AuNP的稳定超分子组装体。将建立共聚物的组成、模型药物或AuNP的存在以及在溶液中形成的共聚物聚集体的形状和尺寸之间的关系。 通过这项研究获得的基础知识将使特定几何形状和尺寸的功能性聚合物纳米结构的需求设计。

Amphiphilic diblock copolymers that are comprised of individual blocks of hydrophobic and hydrophilic repeat units (e.g. AAAAAABBBBBB) can be synthesized such that they self-assemble, under specific conditions, to form aggregates of well-defined shape and size at the nanoscale. At present, there is considerable interest in the production of stable nanotechnologies for use in a wide range of applications in the pharmaceutical and biomedical industries. To this point, it is largely only spherical shaped block copolymer aggregates that have moved forward to commercial development in these industries. For example, in the pharmaceutical industry, a number of anti-cancer drugs relying on formulation in spherical block copolymer micelles have moved into clinical development. However, beyond the spherical shape, amphiphilic copolymers can be engineered to form aggregates with simple, complex and/or hierarchical shapes. Importantly, the shape of copolymer aggregates has a profound impact on their performance such as loading capacity for hydrophobic and hydrophilic cargo, retention of cargo and transport properties in various media. To date, only a small number of established biocompatible copolymers (e.g. polyethylene glycol-block-polycaprolactone (PEG-b-PCL), PEG-b-poly(D,L-lactide) (PEG-b-PLA)) have been shown to reliably form non-spherical shapes, such as worm-like filomicelles' and vesicles, in aqueous solution. Thus, there is an interest in the design of new biocompatible copolymers that enable reproducible production of distinct morphologies in aqueous solution. Beyond encapsulation of hydrophobic and hydrophilic molecules, these amphiphilic block copolymers can be used to organize inorganic, metallic nanoparticles, such as gold nanoparticles (AuNPs) into well-defined 3D architectures. These polymer/metallic hybrid nanostructures possess unique properties and functionality, unattainable with the metallic nanoparticles alone, and have significant potential for use in biomedical applications such as imaging, photothermal therapy, radiation therapy and biosensors. Therefore, this NSERC proposal requests funding to support basic research into the design and development of new amphiphilic, biocompatible materials that enable production of stable supramolecular assemblies, of copolymer and drug or copolymer and AuNPs, of defined shape and dimension. The relationships between the composition of the copolymers, presence of model drug or AuNPs and shape and size of the copolymer aggregates formed in solution will be established. The fundamental knowledge gained through this research will enable on demand design of functional polymeric nanostructures of specific geometries and dimensions.