Well-defined cationic glycopolymers and glyconanoparticles for biomedical applications

该研究项目的重点是设计新型阳离子糖聚合物和糖纳米颗粒，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纳米颗粒最近吸引了大量的关注，因为它们可以表现出与天然存在的糖蛋白和多糖相似的性质。具有连接到其主链上的碳水化合物部分的肽和蛋白质具有许多期望的生物学性质，但它们的化学合成是一个技术挑战。因此，设计可以执行与糖蛋白类似的功能或可以识别糖蛋白的基于碳水化合物的材料是更好地理解细胞识别过程（例如摄取、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应答）的可行方法。设计基于碳水化合物的材料具有若干其他益处，例如改善材料在生理条件下的溶解度，赋予材料生物相容性，以及允许生物分子识别过程。在这项研究计划中，我们的主要重点是探索具有环状碳水化合物残基（如半乳糖残基）的新型糖共聚物和糖纳米颗粒，用于高度特异性的生物分子相互作用和基因递送目的。为了在聚合物和纳米颗粒上提供更多的功能，将共价连接其他生物活性基团以促进特异性结合。研究的另一个重要方面将集中在理解细胞事件和使用这些先进的多功能碳水化合物基纳米材料在细胞内传递基因。除了纳米颗粒表面的糖部分，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.