配位竞争诱导聚合制备非球型中空纳米微粒及其功能化与载药研究

In biomedical applications, polymer hollow anisotropic nanocontainers with various morphologies would significantly affect the adhesion dynamics and uptake efficiency for the target cel,l as a novel drug-delivery vector, which display a great potential in bioimaging and theranostic. In this project, we will focus on the synthesis, functionalization and drug-delivery application of a novel polymer hollow anisotropic nanocontainers, the major research contents include: the polymer hollow anisotropic nanocontainers will be prepared via the method of chelation competition induced polymerization and the universality of the method would be investigated; the synthesis principles and reaction mechanism of chelation competition induced polymerization method will be discussed, the optimal synthesis conditions will be established to control the size, morphology and structure stability of polymer hollow anisotropic nanocontainers; the multifunctional polymer hollow anisotropic nanocontainers (for example fluorescent, magnetic, photodynamic, photothermal and so on)will be constructed through the pre-induction or post-modification of small molecules, ions, and the functional nanoparticles or carbon dots; the loading and release of the drug or imaging agent and the biological safety will be evaluated for the polymer hollow anisotropic nanocontainers, and the research in vitro and in vivo will be carried for the further application of the polymer hollow anisotropic nanocontainers in biomedicine, diagnosis, bioimaging, etc.

非球型中空聚合物纳米微粒的多样拓扑形貌，能够明显影响目标细胞对其的粘附动力学行为和摄取效率，作为一种载体材料，在生物成像以及疾病诊疗方面具有重要的应用前景。本课题主要围绕一种新型载体材料“非球型聚合物中空纳米微粒”的合成、功能化和应用开展基础研究，主要研究内容包括：采用配位竞争诱导聚合方法制备非球型聚合物中空纳米微粒，并对该方法的普适性进行研究；通过对合成条件的精确调控，解决非球型中空微粒结构稳定性差，尺寸形貌难以调控等问题，进一步阐明配位竞争诱导聚合方法的合成规律和反应机理；通过先将功能性纳米微粒引入模板或对中空微粒的表面化学后修饰，制备一系列靶向、荧光、光热或光动力等多功能集成的非球型聚合物中空纳米微粒；开展功能性非球型聚合物中空纳米微粒的生物安全性评价和靶向载药治疗等医学研究，为药物负载和肿瘤诊疗提供一系列新型载体。

中空纳米材料由于特殊的内部空腔结构，在许多领域，如生物医药、光电、催化等方面具有广泛的应用前景。本项目利用一种基于配位竞争诱导聚合（CCIP法）的机理制备非球型中空聚合物纳米结构。该方法利用金属有机框架化合物作为中间体，采用“边拆边聚合”的方式制备中空聚合物纳米结构，条件温和，方法巧妙，为构筑中空聚合物结构提供了研究平台。通过设计实验，理论分析，探讨了金属与单体的结合能、MOFs模板的结构规整性、pH值及溶剂极性等条件对形成聚合物中空结构的影响，明确了配位竞争诱导聚合的合成规律和反应机理；通过引入铁、镍、锰、钯及钛等金属离子或氧化物纳米微粒，利用细胞膜表面修饰或碳化等后处理，赋予聚合物中空纳米微粒丰富的功能性，实现功能性中空微粒的可控制备；利用非球型聚合物中空纳米微粒功能的多样性，开发了其载药、核磁与光声成像、光热治疗等功能在骨修复和肿瘤诊疗等方面的应用；并拓展了其作为氧还原、催化析氢、催化析氧等电催化剂的应用。