低于50nm空心炭球的设计合成及作为血管内皮生长药物载体的缓释性能调控

Hollow carbon spheres (HCSs) have been considered as an ideal drug delivery system due to their many advantages such as high specific surface area, large cavity volume, good biocompatibility, etc. However, it is still a great challenge to synthesize HCSs with size below 50 nm and meanwhile having abundant porosity. This project proposes to synthesize such HCSs using phenolic resin polymer as carbon precursor and oil-in-water emulsion as the template based on the principle of the emulsion polymerization. The loading and controlled release property of the HCSs for vascular endothelial growth factor (VEGF) will be discussed. The research mainly includes the following parts: synthesis of HCSs with size below 50 nm and controlled structures through the assembly of multiple components; creating pores on the carbon shell to match the size of VEGF molecules and then improve the VEGF diffusion rate and tuning the size of hollow cavity to increase the drug loading capacity; functionalization of the inside and outside surface of HCSs and thus increasing the utilization of hollow cavity and strengthening the controlled release property of VEGF. Finally, the project aims to elucidate and understand the formation mechnism of the hollow carbon spheres and the coordinate regulation of their size and structure. Further, this will help to reveal the influencing rules of the structure properties on the loading and controlled release performance of VEGF. This project will provide a scientific basis for the clinical application of VEGF/carbon carrier system and also can provide model materials for study the structure-function relationship of the small size hollow spheres in the fields of catalysis and adsorption.

空心炭球具有比表面积高、空腔大、生物相容性好等优点，是一种理想的药物缓释载体。然而，如何设计合成孔隙发达且粒径小于50 nm的空心炭球仍是该领域面临的挑战。本项目拟借鉴乳液聚合原理，以酚醛树脂基聚合物为前驱体，水包油乳液为模板，控制聚合反应过程动力学，合成粒径均一、具有丰富孔隙结构的空心炭球，并研究其对血管内皮生长因子(VEGF)的负载与控释性能。主要研究内容如下：通过多元组分协同组装构筑粒径小于50 nm的空心炭球并研究其组装规律；在炭球壳壁上创制与VEGF尺寸匹配的孔隙，提高药物扩散速率，同时调变空腔大小以增加药物负载量；对空心炭球进一步功能化，提高空腔利用率，强化VEGF的受控释放性能。项目将从微观层面上理解炭球粒径和孔隙的协同调控机制，揭示炭球结构等对VEGF负载及控释性能的影响规律，为载药纳米炭的应用研究提供科学依据，也为研究小尺寸空心球在催化、吸附等领域的构效关系提供模型材料。

纳米空心炭球除了具有多孔炭固有的比表面积高、孔隙丰富、生物相容性好、理化性质稳定等优点之外，还具有各向同性、空腔体积大和密度相对较低的特点，可广泛应用于生物医药、能源存储与转化以及吸附分离等领域。本项目从对炭材料形成过程认识出发，创新空心炭球的合成方法，以酚醛树脂为聚合物前驱体，通过调控反应过程中催化剂的种类和用量，反应温度及表面活性剂的用量，平衡平衡聚合反应速率及其表面能，实现聚合物球粒径的调控，进一步利用聚合物炭化过程中粒径收缩及碳质物质释放的特性，结合纳米空间限域效应制备了具有不同空心状态的炭球；拓展上述合成方法，制备了孔隙结构可控的介孔炭材料、粒径和形貌可控的二氧化锡及晶粒细化的纳米锌镍合金，并研究了其在锂硫电池、锂离子电池、防腐等领域中的应用；利用聚多巴胺对空心炭球进行修饰并研究其对EGF的吸附和缓释性能，初步探索载有EGF的空心炭球在细胞和离体心脏中的响应性能；以2,2-联吡啶对介孔炭炭材料进行功能化，强化其在吸附、催化及储能领域的应用性能。在本项目的资助下，研究成果在Materials Letter、Nano等期刊发表SCI论文收录4篇，项目负责人顺利完成博士后研究并出站，职称由讲师晋升为副教授，另有参与人员两名博士生、一名本科生完成学位论文答辩。