Advanced Polymers and Nanocarriers for Nanomedicine

本研究计划的重点是发展纳米药物的先进纳米载体。新型纳米载体的发展及其在给药领域的重要应用与高分子化学研究的进展直接相关。新型阳离子聚合物和纳米颗粒的合成具有改进的基因传递效率是这种纳米载体的一个例子。合成纳米载体在纳米医学领域的巨大成功促使我们设计一种具有强大抗菌、基因和药物传递功能的多功能聚合物载体平台。我们提出的聚合物载体平台由两个主要部分组成；A)具有抗菌性能的新型生物相容性部分和b)线性和分支结构的含有阳离子部分的多胺。生物分子功能化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，维生素B5基材料的合成并不多见，仅有少数报道讨论了维生素B5基材料在组织工程中的应用。维生素B5是一种水溶性分子，是哺乳动物和细菌代谢的重要组成部分。维生素B5结构的微小变化已知会对细菌活力造成致命影响，而对哺乳动物细胞活力没有显著变化。由于维生素B5基材料的这些多功能特性，我们认为维生素B5基聚合物载体将是理想的聚合物载体，同时具有抗菌和基因和药物传递能力。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，阳离子载体的理化性质在很大程度上决定了其生物学结果（如毒性和基因传递效果）。聚乙烯亚胺（PEI）是一种众所周知的基因传递载体，它由一级胺、二级胺和叔胺组成，这些胺在PEI中的组合可以增强这种聚合物的基因表达。据我们所知，用可逆加成裂解链转移（RAFT）聚合方法聚合含多胺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类似单体和含有线性和支链结构的RAFT活性单体，然后通过RAFT方法进行同源和共聚，从而得到具有预定分子量、结构和组成的明确定义的聚合物和纳米颗粒。获得的聚合物平台将在体外研究中测试其基因和药物传递效率以及抗菌性能。

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.