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

背景：具有高生物相容性和多种功能的材料在药物传递和疾病检测等生物医学应用中非常重要。然而，当单独使用时，现有的材料，如聚合物或无机纳米颗粒，不能提供所需的性能和功能。因此，我们建议开发具有多种功能和最佳性能的新型聚合物和聚合物-无机杂化材料。本研究是对申请人以前和目前工作的扩展和延续。这项研究的长期目标是推动设计和开发用于控制药物输送和生物医学成像的新型聚合物、聚合物-脂质和聚合物-无机系统的科学和技术。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无创成像进行疾病检测。本项目的具体目标是：(1)研究生物相容性聚合物与蛋白质药物的分子相互作用，并通过CG-MD模型选择领先聚合物。通过CG-MD模型和分子对接模拟，我们将了解合成聚合物（如三嵌段共聚物和两性离子聚合物）稳定蛋白质药物（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进行蛋白质配方设计。(2)合成经obj鉴定的新型聚合物。并通过实验考察其对蛋白质药物的稳定作用。不同组成的蛋白质-聚合物配方将通过高效液相色谱和CD进行检测，然后通过糖尿病大鼠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共轭三元聚合物纳米颗粒，用于脑内病毒感染的MR成像。(4)设计新型ph响应型两亲性聚合物微凝胶，结合抗菌抗体和荧光染料，用于光学成像现场检测细菌感染。该项目将由DND/NSERC补充拨款支持，并将由DND委员会单独审查。新颖性和意义：所提出的多功能聚合物和聚合物-无机纳米复合材料尚未见报道。所开发的新材料将在生物医学应用中显示出有用的特性，并将推动生物材料在药物输送和医学成像方面的科学和技术。尽管它们在生物医学上有应用，但新材料的合成和表征将不会得到诸如CIHR这样的卫生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.