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（例如 AAAAAABBBBBB）的各个嵌段组成的两亲性二嵌段共聚物，使得它们在特定条件下自组装，形成纳米级形状和尺寸明确的聚集体。目前，人们对生产稳定的纳米技术产生了很大的兴趣，以广泛应用于制药和生物医学行业。到目前为止，这些行业中基本上只有球形嵌段共聚物聚集体已进入商业开发。例如，在制药行业，许多依靠球形嵌段共聚物胶束配方的抗癌药物已进入临床开发。然而，除了球形之外，两亲性共聚物还可以被设计成形成具有简单、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其性能具有深远的影响，例如疏水性和亲水性货物的装载能力、货物在各种介质中的保留和运输性能。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））被证明能够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，人们对设计新型生物相容性共聚物感兴趣，这种共聚物能够在水溶液中重复产生不同的形态。除了封装疏水性和亲水性分子之外，这些两亲性嵌段共聚物还可用于将无机金属纳米颗粒（例如金纳米颗粒 (AuNP)）组织成明确的 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，是单独使用金属纳米粒子无法实现的，并且在成像、光热疗法、放射疗法和生物传感器等生物医学应用中具有巨大的应用潜力。因此，NSERC 的这项提案请求资金支持新型两亲性、生物相容性材料的设计和开发的基础研究，这些材料能够生产具有确定形状和尺寸的稳定的超分子组件，包括共聚物和药物或共聚物和金纳米粒子。将建立共聚物的组成、模型药物或 AuNP 的存在以及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能够按需设计特定几何形状和尺寸的功能性聚合物纳米结构。

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.