Multifunctional intelligent polymers and polymer-inorganic hybrid materials for biomedical applications

背景资料：具有高生物相容性和多功能性的材料对于包括药物递送和疾病检测在内的生物医学应用非常重要。然而，当单独使用时，现有的材料，如聚合物或无机纳米颗粒，不能提供所需的性质和功能。因此，我们建议开发新的聚合物和聚合物-无机杂化材料，将提供多种功能和最佳性能。 这项拟议的研究是申请人以前和目前工作的扩展和延续。本研究的长期目标是推进新型聚合物、聚合物-脂质和聚合物-无机系统的设计和开发的科学和技术，用于药物控释和生物医学成像。短期目标是开发新型多功能智能聚合物和聚合物-无机材料，用于有效的药物输送和通过非侵入性成像进行疾病检测。 该项目的具体目标是： (1)通过分子动力学模拟研究生物相容性高分子与蛋白质药物的分子相互作用，筛选先导高分子。从CG-MD建模和分子对接模拟中，我们将了解合成聚合物（例如三嵌段共聚物和两性离子聚合物）稳定蛋白质药物（例如胰岛素和胰高血糖素）的机制。根据模拟结果，我们将选择或合成新的聚合物用于蛋白质配方设计。 (2)合成目标1中确定的新型聚合物，并通过实验研究其对蛋白质药物的稳定作用。将通过HPLC和CD检查不同组成的蛋白质-聚合物制剂，然后通过糖尿病大鼠中的葡萄糖调节活性测定。 (3)设计具有螯合顺磁性金属离子的抗病毒抗体缀合的纳米颗粒，用于脑部病毒感染的MR成像。 (4)设计新型pH响应性两亲性聚合物微凝胶颗粒，其具有缀合的抗菌抗体和荧光染料，用于通过光学成像进行细菌感染的现场检测。该项目将由DND/NSERC补充补助金支持，并将由DND委员会单独审查。 新奇和意义：提出的多功能聚合物和聚合物-无机纳米复合材料以前没有报道。所开发的新材料将显示出用于生物医学应用的有用特性，并将推进用于药物递送和医学成像的生物材料的科学和技术。尽管它们具有生物医学应用，但新材料的合成和表征将不会得到CIHR等健康研究资助机构的资助。

Background: Materials with high biocompatibility and multiple functionalities are very important for biomedical applications including drug delivery and disease detection. However, when used alone, existing materials, such as polymers or inorganic nanoparticles, cannot provide desired properties and functionalities. Thus we propose to develop novel polymers and polymer-inorganic hybrid materials that will provide multiple functions and optimal properties. This proposed research is an expansion and continuation of the applicant's previous and current work. The long-term goal of this research is to advance the science and technology of the design and development of novel polymers, polymer-lipid and polymer-inorganic systems for controlled drug delivery and biomedical imaging. The short-term goal is to develop novel multifunctional intelligent polymers and polymer-inorganic materials for effective drug delivery and disease detection by non-invasive imaging. The specific objectives in this project are: (1) Study the molecular interactions between biocompatible polymers and protein drugs and select leading polymers by CG-MD modeling. From the CG-MD modeling and molecular docking simulation, we will understand the mechanism by which synthetic polymers (e.g. triblock copolymers and zwitterionic polymers) stabilize protein drugs, e.g. insulin and glucagon. Based on the simulation results, we will select or synthesize new polymers for the protein formulation design. (2) Synthesize novel polymers identified in obj.1 and investigate their effect on stabilizing the protein drugs by experiments. Protein-polymer formulations of varying compositions will be examined by HPLC and CD, and then by glucose-regulation activity assay in diabetic rats. (3) Design anti-viral antibody-conjugated terpolymer nanoparticles with chelated paramagnetic metal ions for MR imaging of viral infections in the brain. (4) Design novel pH-responsive amphiphilic polymer microgel particles with conjugated anti-bacterial antibodies and fluorescent dyes for on-site detection of bacterial infections by optical imaging. This project will be supported by the DND/NSERC Supplemental Grant and will be reviewed separately by DND committee. Novelty and Significance: The proposed multifunctional polymers and polymer-inorganic nanocomposite materials have not been reported before. The developed new materials will exhibit useful properties for biomedical applications and will advance the science and technology of biomaterials for drug delivery and medical imaging. Despite their biomedical applications, the synthesis and characterization of new materials will not be funded by health research funding agencies such as CIHR.