Well-defined cationic glycopolymers and glyconanoparticles for biomedical applications

本研究计划的重点是设计新型阳离子糖共聚物和糖聚糖颗粒，用于生物分子识别过程和基因传递应用的研究。合成的糖共聚物和糖聚糖颗粒近年来引起了人们的广泛关注，因为它们具有与天然存在的糖蛋白和多糖相似的性质。带碳水化合物的多肽和蛋白质具有许多理想的生物学特性，但它们的化学合成是一个技术挑战。因此，设计具有与糖蛋白相似功能或能够识别糖蛋白的碳水化合物基材料是更好地理解细胞识别过程（如摄取、细胞生长调节、分化、粘附、细胞运输、细菌和病毒的炎症以及免疫反应）的可行方法。设计碳水化合物基材料还有其他一些好处，如提高材料在生理条件下的溶解度，赋予材料的生物相容性，并允许生物分子识别过程。在这个研究项目中，我们的主要重点是探索具有环碳水化合物残基（如悬垂的半乳糖残基）的新型糖共聚物和糖聚糖颗粒，用于高度特异性的生物分子相互作用和基因传递目的。为了在聚合物和纳米颗粒上提供更多的功能，其他生物活性基团将以共价方式附着以促进特异性结合。研究的另一个重要方面将集中在利用这些先进的多功能碳水化合物纳米材料了解细胞事件和基因在细胞内的传递。除了纳米颗粒表面的糖基团外，我们还计划整合磷酰胆碱基团以增强纳米颗粒的生物亲和性，并防止不利的非特异性结合。

This research program is focused towards the design of novel cationic glycopolymers and glyconanoparticles for the study of biomolecular recognition processes and gene delivery applications. Synthetic glycopolymers and glyconanoparticles have attracted a great deal of attention lately as they can exhibit similar properties to naturally occurring glycoproteins and polysaccharides. Peptides and proteins with carbohydrate moieties attached to their backbone have many desirable biological properties, but their chemical synthesis is a technical challenge. Therefore, designing carbohydrate based materials that can perform similar functions as glycoproteins or can recognize glycoproteins is a viable approach for better understanding of the cellular recognition processes such as uptake, cell growth regulation, differentiation, adhesion, cellular trafficking, inflammation by bacteria and viruses and the immune response. Designing carbohydrate based materials have several other benefits such as improving the solubility of the materials in physiological conditions, imparting biocompatibility in the materials, and allowing biomolecular recognition processes. In this research program, our primary focus is to explore novel glycopolymers and glyconanoparticles with cyclic carbohydrate residues (such as pendent galactose residues) for highly specific biomolecular interactions and for gene delivery purposes. To provide more functionality on the polymers and nanoparticles, other bioactive groups will be attached covalently to promote specific binding. Another important aspect of the research will focus on understanding cellular events and delivery of gene inside cells using those advanced multi-functional carbohydrate based nano-materials. In addition to the saccharide moieties on the surface of the nanoparticles, we also plan to integrate phosphoryl choline groups for enhanced bioaffinity of the nanoparticles and to prevent unfavorable non-specific binding.