基于瓜环的高分子纳米胶囊递药系统的构建及评价

高分子纳米胶囊是一种具有空心结构的纳米粒子，在药物递送过程中表现出了传统纳米载体无法比拟的优势。以刚性大环分子为单元构筑的二维共价交联高分子网络结构在表面张力驱动下自组装而成的纳米胶囊，因其可通过表面大环的主客体组装进行多功能修饰，在药物递送领域有广阔的应用前景。针对当前基于大环分子构建的高分子纳米胶囊存在的生理环境稳定性不理想、应激响应性单一及治疗模式单一等关键科学问题，本课题拟利用六元瓜环衍生物分别构建活性氧响应型、乏氧响应型、谷胱甘肽响应型及光动力型等纳米胶囊，并利用瓜环超强的主客体作用介导的组装对纳米胶囊表面进行多功能修饰，进一步构筑新型多功能纳米胶囊药物递送系统，实现靶向给药、控制释放、多模式协同治疗等多功能。本课题拟研究这些新型的基于大环的高分子纳米胶囊的制备方法及其优化，并对纳米胶囊的微观结构、应激响应性、功能性、载释药特性、生物相容性、及体外治疗效果等进行体统评价。

Polymeric nanocapsules (NCs), possessing a hollow interior, have shown various advantages over traditional nano-carriers for drug delivery. In particular, NCs formed via self-assembly of covalently crosslinked macrocycles-based 2D polymer network have shown significant potential in drug delivery, as macrocycles on the surface of NCs can be readily decorated with various functional tags through host-guest interactions. Aiming at addressing several key scientific issues faced by macrocycle-based polymer nanocapsules (NCs) for drug delivery, including unsatisfactory physiological stability, lack of diverse stimuli-responsiveness, and single therapeutic modality, herein we propose to leverage cucurbit[6]uril (CB[6]) derivatives to construct ROS-, hypoxia-, GSH-, and photo-responsive polymer NCs, respectively. Endowed with versatile surface functionality via noncovalent interactions between CB[6] and spermine-conjugated functional tags, several multifunctional drug delivery systems will be designed and developed for targeted delivery, controlled drug release, and multi-modality synergistic cancer therapy. The preparation methods and process leading to novel NCs will be developed and optimized in this study, and their structures, stimuli-responsiveness, functionality, drug loading/release profiles under different conditions, biocompatibility and therapeutic efficacy in vitro will be systemically investigated.