Engineering Block Copolymer and Hybrid Nanotechnologies of Well-Defined Architecture

由单独的疏水和亲水重复单元(例如AAAAAABBBBB)组成的两亲性两嵌段共聚物可以被合成，使得它们在特定条件下自组装成纳米尺度上定义良好的形状和大小的聚集体。目前，人们对生产稳定的纳米技术非常感兴趣，这些技术在制药和生物医学行业的广泛应用中使用。到目前为止，很大程度上只是球形嵌段共聚聚合物聚集体在这些行业中走向了商业开发。例如，在制药行业，一些依靠球形嵌段共聚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有深刻的影响，如疏水和亲水货物的装载能力，货物在各种介质中的保持性和运输性能。到目前为止，只有一小部分已建立的生物相容性共聚物(例如聚乙二醇嵌段聚己内酯(PEGb-PCL)、聚乙二醇聚(D，L-丙交酯)(PEGb-PLAC))在水溶液中可靠地形成非球形，如蠕虫状的丝状胶束和囊泡。因此，人们对设计新的生物相容性共聚物感兴趣，这种共聚物能够在水溶液中重复生产不同的形态。除了包裹疏水和亲水分子外，这些两亲性嵌段共聚物还可以用来将无机金属纳米粒子，如金纳米粒子(AuNPs)组织成明确的3D结构。这些聚合物/金属杂化纳米结构具有单独的金属纳米颗粒无法实现的独特的性质和功能，在成像、光热治疗、放射治疗和生物传感器等生物医学应用中具有巨大的潜力。因此，NSERC的这项提案要求提供资金，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，这些材料能够生产稳定的超分子组件，即定义形状和尺寸的共聚物和药物或共聚物和AuNPs。共聚物的组成、模型药物或AuNPs的存在以及在溶液中形成的共聚物聚集体的形状和大小之间的关系将被建立。通过这项研究获得的基本知识将使按需设计特定几何和尺寸的功能聚合物纳米结构成为可能。

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.