Bioorthogonal Nanodiamond / Glycopolymer Hybrid Design to Simulate the Structure of Viruses

该提案的目的是在纳米颗粒上产生受大自然启发的糖共聚物表面化学物质。受病毒入侵细胞成功的激励，我们的目标是通过温和的光诱导正交反应，利用高效的聚合物接枝方法模拟病毒的表面结构。为了实现这一具有挑战性的目标，我们融合了Stenzel教授（糖共聚物应用、纳米颗粒设计、细胞相互作用）和Barner-Kowollik教授（先进聚合物合成、光诱导连接方案、复杂大分子表面设计）的专业知识。病毒-细胞表面相互作用的关键在于糖蛋白在其表面的特定排列，这些糖蛋白通常以天线状结构组织。这些糖蛋白以高度特异性的方式与细胞表面的受体相互作用。在目前的提议中，模仿天然多糖结构的生物活性的糖共聚物将通过温和有效的光诱导化学反应接枝到纳米金刚石上。采用纳米金刚石作为病毒模板的优点是它们的非漂白荧光和无毒性，允许在荧光显微镜下研究糖共聚物包被的纳米颗粒，因此可以进行长期的细胞相互作用研究。为了获得与病毒相似的结构，糖共聚物将与反应性聚合物共接枝，生成合成病毒。当前提案的最终目的是提高关于糖共聚物颗粒与哺乳动物细胞相互作用的知识。我们试图了解需要何种类型的糖共聚物表面来增强与表面受体的相互作用并最终促进细胞摄取。

The aim of the proposal is to generate glycopolymer surfaces chemistries on nanoparticles that are inspired by nature. Motivated by the success of viruses to invade cells, we aim at mimicking the virus' surface structure using an efficient polymer grafting approach via mild light-induced orthogonal reactions. To achieve this challenging goal, we fuse the expertise of Prof. Stenzel (glycopolymer applications, nanoparticle design, cellular interactions) and Prof. Barner-Kowollik (advanced polymer synthesis, light-induced ligation protocols, complex macromolecular surface design). The key to virus-cell surface interactions lies in the specific arrangement of glycoproteins on their surface, which are often organized in an antennae-like structure. These glycoproteins interact in a highly specific fashion with receptors on the surfaces of cells. In the current proposal, glycopolymers that imitate natural polysaccharide structures in terms of bioactivity will be grafted onto nanodiamonds via mild and effective light-induced chemistries. The advantage of employing nanodiamonds as virus-templates is their non-bleaching fluorescence and non-toxicity that allows the study of the glycopolymer coated nanoparticles under a fluorescent microscope and therefore enables long-term cell-interaction studies. In order to achieve structures similar to the one found on viruses, the glycopolymers will be co-grafted with responsive polymers generating synthetic viruses. The ultimate aim of the current proposal is the advancement of knowledge regarding the interaction of glycopolymer particles with mammalian cells. We seek to understand what type of glycopolymer surface is required to enhance the interaction with the receptors on the surface and to ultimately promote cellular uptake.