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

生物正交纳米金刚石/糖聚合物杂化设计模拟病毒结构

• 批准号: 271285424
• 负责人: Professor Dr. Christopher Barner-Kowollik
• 金额: --
• 依托单位: School of Chemical Engineering
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/271285424?language=en
• 关键词: Bioorthogonal; Nanodiamond; Glycopolymer; Hybrid; Design

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.

该提议的目的是在受自然启发的纳米颗粒上产生糖共聚物表面化学物质。受病毒成功入侵细胞的激励，我们的目标是通过温和的光诱导正交反应，使用一种高效的聚合物接枝方法来模拟病毒的表面结构。为了实现这一具有挑战性的目标，我们融合了斯坦泽尔教授(糖共聚物应用、纳米颗粒设计、细胞相互作用)和巴纳-科沃利克教授(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其表面糖蛋白的特殊排列，这些糖蛋白通常以触角状结构组织起来。这些糖蛋白以高度特异的方式与细胞表面的受体相互作用。在目前的提议中，在生物活性方面模仿天然多糖结构的糖共聚物将通过温和而有效的光诱导化学反应嫁接到纳米钻石上。使用纳米钻石作为病毒模板的优势是其不漂白的荧光和无毒性，这使得可以在荧光显微镜下研究糖共聚物包裹的纳米颗粒，从而能够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，糖共聚物将与产生合成病毒的响应性聚合物共同嫁接。目前这项提议的最终目的是促进关于糖共聚物颗粒与哺乳动物细胞相互作用的知识的发展。我们试图了解哪种类型的糖共聚物表面需要增强与表面受体的相互作用，并最终促进细胞摄取。

项目成果

Fluorescent Glyco Single-Chain Nanoparticle-Decorated Nanodiamonds.

• DOI: 10.1021/acsmacrolett.7b00659
• 发表时间: 2017-10
• 期刊: ACS macro letters
• 影响因子: 5.8
• 作者: Kilian N. R. Wuest;Hongxu Lu;Donald S. Thomas;Anja S. Goldmann;M. Stenzel;C. Barner‐Kowollik

Direct light-induced (co-)grafting of photoactive polymers to graphitic nanodiamonds

光敏聚合物直接光诱导（共）接枝到石墨纳米金刚石上

• DOI: 10.1039/c6py02035f
• 发表时间: 2017
• 期刊: Polymer Chemistry
• 影响因子: 4.6
• 作者: K. N. R;Trouillet;Köppe;Roesky;Goldmann;Stenzel;Barner-Kowollik
• 通讯作者: Barner-Kowollik

Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.

• DOI: 10.1021/acs.biomac.6b00754
• 发表时间: 2016-07
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: Jiacheng Zhao;H. Lai;Hongxu Lu;C. Barner‐Kowollik;M. Stenzel;P. Xiao

Delivery of Amonafide from Fructose-Coated Nanodiamonds by Oxime Ligation for the Treatment of Human Breast Cancer.

• DOI: 10.1021/acs.biomac.7b01592
• 发表时间: 2018-01
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: Jiacheng Zhao;Mingxia Lu;H. Lai;Hongxu Lu;J. Lalevée;C. Barner‐Kowollik;M. Stenzel;P. Xiao

Polymer Functional Nanodiamonds by Light-Induced Ligation

• DOI: 10.1021/acs.macromol.5b02607
• 发表时间: 2016-02
• 期刊: Macromolecules
• 影响因子: 5.5
• 作者: Kilian N. R. Wuest;V. Trouillet;Anja S. Goldmann;M. Stenzel;C. Barner‐Kowollik