Advanced Polymers and Nanocarriers for Nanomedicine

这项研究计划专注于开发用于纳米医学的先进纳米载体。新型纳米载体的发展及其在药物递送应用中的重大贡献直接关系到聚合物化学领域研究人员的进步。具有改进的基因传递效率的新型阳离子聚合物和纳米颗粒的合成就是这种纳米载体的一个例子。人工合成纳米载体在纳米药物领域的巨大成功促使我们设计了一种新型的多功能聚合物载体平台，具有强大的抗菌、基因和药物输送效率。我们提出的聚合物载体平台由两个主要部分组成：a)具有抗菌性能的新的生物相容部分和b)含有线状和支化结构的阳离子部分的多胺。生物分子功能化的聚合物载体被广泛研究以赋予合成载体生物相容性。在生物分子功能化材料中，基于维生素的材料的合成并不常见，只有少数报告讨论了基于维生素B5的材料在组织工程中的应用。维生素B5是一种水溶性分子，是哺乳动物和细菌新陈代谢的重要组成部分。众所周知，维生素B5结构的轻微变化会对细菌的生存能力造成致命影响，而对哺乳动物细胞的生存能力没有显著影响。由于基于维生素B5的材料的这些多功能属性，我们认为基于维生素B5的聚合物载体将是具有同时抗菌和基因和药物输送能力的理想的聚合物载体。同样，阳离子组分的选择是我们材料成功的关键因素。对阳离子聚合物基因传递能力的研究表明，阳离子载体的物理化学性质在很大程度上决定了它们的生物结果(如毒性和基因传递效率)。聚乙烯亚胺(PEI)是一种著名的基因递送载体，它由伯胺、仲胺和叔胺组成，这些胺在PEI中的组合被发现可以增强这种聚合物的基因表达。据我们所知，通过可逆加成断裂链转移(RAFT)聚合来聚合含多胺的阳离子单体尚未见报道。为了开发多功能纳米载体，我们的目标是制备维生素B5类似物单体和含有多个胺的直链和支链结构的RAFT活性单体，然后通过RAFT方法进行均聚和共聚，得到预定分子量、结构和组成的定义良好的聚合物和纳米颗粒。获得的聚合物平台将在体外研究期间测试其基因和药物输送效率以及抗菌性能。

This research program focuses on the development of advanced nanocarriers for nanomedicines. The development of novel nanocarriers and their significant contribution in drug delivery applications is directly related to the progress of researchers in field of polymer chemistry. The synthesis of novel cationic polymers and nanoparticles with improved gene delivery efficacies are one example of such nanocarriers. The significant success of synthetic nanocarriers in field of nanomedicines encouraged us to design a novel multifunctional platform of polymeric vectors with potent antibacterial and gene and drug delivery efficacies. Our proposed platform of polymeric carriers is composed of two main components; a) novel biocompatible moiety with antibacterial properties and b) multiple amine containing cationic moieties of linear and branched architectures. Biomolecules functionalized polymeric carriers are well-studied to impart biocompatibility to synthetic vectors. Among biomolecule-functionalized materials, synthesis of vitamin based materials are uncommon and only handful of reports discuss the used of vitamin B5 based materials for tissue engineering applications. Vitamin B5 is a water-soluble molecule and is an important component of mammalian and bacterial metabolism. The slight changes in structure of vitamin B5 are known to cause lethal impact on bacterial viability, with no significant changes in mammalian cell viability. Owing to these multifunctional attributes of vitamin B5 based materials, we argue that vitamin B5 based polymeric vectors will be ideal polymeric carriers with simultaneous antibacterial and gene and drug delivery capabilities. Similarly, the choice of cationic component is a critical factor for success of our materials. The research on gene delivery capabilities of cationic polymers reveals that physiochemical properties of cationic vectors largely dictate their biological outcomes (such as toxicity and gene delivery efficacies). Polyethyleneimine (PEI) is a well-known gene delivery vectors, which is composed of primary, secondary and tertiary amines and combination of these amines in PEI is found to enhance the gene expression of this polymer. To the best of our knowledge, polymerization of multiple amine containing cationic monomers by reversible addition fragmentation chain transfer (RAFT) polymerization is not yet reported. In order to develop multifunctional nanocarriers, we aim to prepare vitamin B5 analogous monomer and multiple amine containing RAFT active monomers of linear and branched architectures followed by their homo and copolymerization by RAFT approach to yield well-defined polymers and nanoparticles of predetermined molecular weight, architecture and compositions. The platforms of polymers obtained will be tested for their gene and drug delivery efficacies and antibacterial properties during in vitro studies.