Molecularly Imprinted Core-Shell Nanoparticles / understanding fundamentals and developing applications based on biorecognition

分子印迹核壳纳米颗粒/了解基础知识并开发基于生物识别的应用

• 批准号: BB/D011949/1
• 负责人: Andrew Mayes
• 金额: $ 27.04万
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD011949%2F1
• 关键词: Molecularly; Imprinted; Core; Shell; Nanoparticles

Biological proteins, such as antibodies and a bacterial protein called streptavidin, are widely used in developing assays to measure both large (e.g. proteins that indicate disease states such as the presence of a virus) and small molecules (e.g. drugs or pesticides). Such assays are used in clinical diagnosis, environmental monitoring, forensic analysis and also in home diagnostic products such as pregnancy test kits. While these proteins work well, they are generally very expensive to produce and are not very stable, which limits the shelf-life of products and often means that they have to be carefully stored (e.g. in a refrigerator). This is a major problem for product developers, particularly if the product will be used in third world environments. It would be a huge technological breakthrough if these fragile biological molecules could be replaced by robust synthetic analogues that had the same function as the antibodies, but were inexpensive to produce and stable in storage. Over the last few years a technique has been developed called 'molecular imprinting', which allows materials with antibody-like properties to be produced quickly and cheaply in plastic materials. These 'molecularly imprinted polymers - MIPs' are made by a process much like molecular scale plaster casting. Monomers (the building blocks of the polymer) are assembled around a molecular template and are then polymerised to make the polymer. Once the polymer is cured, the template can be removed to leave a moulded molecular receptor that is capable of rebinding the template with a high degree of precision. MIPs are extremely robust and can be stored almost indefinitely at room temperature without loss of fuction. The problem with current MIPs is that they are generally made in the form of large blocks, which are then crushed up into tiny particles for use. These particles are very big compared with biological molecules such as proteins, however, and this leads to many problems when trying to use MIPs for developing assays, such as very slow transport of molecules through the MIPs or inability of larger molecules to penetrate into the plastic structure at all. It would be much better if the MIPs could be made at the nano-scale (1 nm = 1 milionth of 1 mm) / a similar size to that of proteins, viruses etc., so that mixing with biological molecules could be very rapid. Recently, our group has developed a method to make MIPs at such a scale, which we believe will be applicable to imprinting of a wide range of different types of molecules with different properties. This method involves creating the MIP in a thin shell around the surface of a polymer nanoparticle / a so-called core-shell nanoparticle. This particular format is very exciting because the core of the nanoparticle can be designed to have useful properties that make the particles easier to see (e.g. it might fluoresce when irradiated with light of a particular wavelength) or manipulate (e.g. it might be magnetic, so that the nanoparticles can be extracted easily from a solution using a magnet). These properties are very useful in the design of particular assays or analytical reagents. The moulded receptor sites would be at or very near to the surface of the very thin shell around the nanoparticle, where they can easily interact with the target molecule or bind to a surface where the target molecule is found. The aim of this project is to investigate whether this approach to synthesising core-shell MIP nanoparticles can lead to new types of cheap, robust bio-mimetic reagents that can be used as substitutes for antibodies or other biological proteins in assays and diagnostic tests.

生物蛋白质，如抗体和一种称为链霉亲和素的细菌蛋白质，广泛用于开发测定大分子（如指示疾病状态的蛋白质，如病毒的存在）和小分子（如药物或农药）的测定。此类测定用于临床诊断、环境监测、法医分析以及家用诊断产品，如妊娠测试试剂盒。虽然这些蛋白质的效果很好，但它们的生产通常非常昂贵，并且不太稳定，这限制了产品的保质期，通常意味着它们必须小心储存（例如在冰箱中）。这对产品开发人员来说是一个主要问题，特别是如果产品将用于第三世界环境。如果这些脆弱的生物分子可以被具有与抗体相同功能的强大合成类似物所取代，这将是一个巨大的技术突破，但生产成本低，储存稳定。在过去的几年里，一种名为“分子印迹”的技术已经开发出来，它允许在塑料材料中快速而廉价地生产具有类似抗体特性的材料。这些“分子印迹聚合物”是由一个过程很像分子规模石膏铸造。单体（聚合物的构建单元）围绕分子模板组装，然后聚合以制造聚合物。一旦聚合物被固化，模板可以被移除以留下能够以高精度重新结合模板的模制分子受体。MIPs非常耐用，几乎可以在室温下无限期储存而不会失去功能。目前的MIP的问题在于，它们通常以大块的形式制成，然后将其粉碎成微小的颗粒以供使用。然而，与生物分子如蛋白质相比，这些颗粒非常大，并且当试图使用MIP进行开发测定时，这导致许多问题，例如分子通过MIP的传输非常缓慢，或者较大分子根本不能渗透到塑料结构中。如果MIP可以在纳米尺度（1 nm = 1 mm的1百万分之一）/与蛋白质、病毒等类似的尺寸下制备，这样与生物分子的混合就可以非常迅速。最近，我们的小组已经开发出一种方法，使分子印迹聚合物在这样的规模，我们相信这将适用于印迹的各种不同类型的分子具有不同的属性。该方法涉及在聚合物纳米颗粒/所谓的核-壳纳米颗粒的表面周围的薄壳中产生MIP。这种特殊的形式是非常令人兴奋的，因为纳米颗粒的核心可以被设计为具有有用的特性，使颗粒更容易看到（例如，当用特定波长的光照射时，它可能会发出荧光）或操纵（例如，它可能是磁性的，因此可以使用磁铁从溶液中轻松提取纳米颗粒）。这些性质在特定测定或分析试剂的设计中非常有用。模制受体位点将位于或非常接近纳米颗粒周围非常薄的壳的表面，在那里它们可以容易地与靶分子相互作用或结合到发现靶分子的表面。稳健的生物模拟试剂，其可在测定和诊断测试中用作抗体或其它生物蛋白的替代物。

项目成果

Preparation of Polymeric Core-Shell and Multilayer Nanoparticles: Surface-Initiated Polymerization Using in Situ Synthesized Photoiniferters

• DOI: 10.1021/ma9019812
• 发表时间: 2010-01-26
• 期刊: MACROMOLECULES
• 影响因子: 5.5
• 作者: Ali, A. M. Imroz;Mayes, Andrew G.
• 通讯作者: Mayes, Andrew G.

Understanding and preventing the formation of deformed polymer particles during synthesis by a seeded polymerization method

• DOI: 10.1002/pola.24636
• 发表时间: 2011-05
• 期刊: Journal of Polymer Science Part A
• 作者: Anong Srisopa;A. Ali;A. Mayes