纳米沉淀法精确制备天然来源聚合物仿生纳米胶囊的策略研究

Thanks to specific bio-functions of component polymers, natural-origin polymers based nanocapsules having cell-mimetic “core-shell” structure, have been in the spotlight on exploration of complex cell-function and construction of advanced nano-materials. Nanoprecipitation is a low-cost spontaneous emulsification, showing high controllability and wide substrate-range. Most of polymers and small molecules without any modification are able to self-assemble into well-defined nanoparticles under nanoprecipitation. In our study, natural-origin polysaccharides and proteins are more interesting for specific structures and powerful bio-functions. However, considering of high electrical density and hydrogen bonding, they are not suitable to conventional nanoprecipitation. Therefore, we firstly propose a new method to trigger the spontaneous emulsification of polysaccharides and proteins into nanoparticles, and elaborate the mechanism and process of emulsification, then analyze the self-assembly process of polymers and structure of aggregates. According to the physical chemical properties of formed emulsions at different solution compositions, we enable to carefully establish the polymer/solvent/non-solvent ternary phase diagrams, which can precisely guide us to construct series of dimension and structure controllable natural-origin polymers based nanocapsules under “one-pot” nanoprecipitation. We finally investigate the bio-functions of bio-mimetic nanocapsules and systematically evaluate their potentials in biomedical application. Achievement of this study discloses a new strategy in construction of natural-origin polymers based biomimetic nanocapsules, revealing its significance in expanding the application of nanoprecipitation and exploring advanced nano-materials.

天然来源聚合物纳米胶囊，拥有类似细胞的“核-壳”结构，因其组成聚合物特异的生物功能，使其成为研究细胞复杂生物学机理和构建先进功能纳米材料的重要研究对象。纳米沉淀法作为低能耗的自发乳化方法，具有高度可控性和广泛底物适应性，其可将聚合物和小分子无需结构修饰一步自组装转化为纳米颗粒。本项目选取天然来源的聚糖和蛋白为研究对象，提出针对高电荷密度和高氢键强度聚合物的纳米沉淀新的触发方法，揭示新方法自发乳化的原理和过程，分析聚合物自组装过程和结构，研究不同溶液条件下乳液的物理化学性质，以此为基础准确构建出聚合物/溶剂/非溶剂的三相图，并以相图为指导利用纳米沉淀法“一锅”制备一系列尺寸和结构精确可控的天然来源聚合物纳米胶囊，系统性评估所制备具有仿生结构的功能纳米胶囊在生物医药领域的应用潜力。本项目研究对开发纳米沉淀的应用潜力和探索先进仿生纳米材料都具有重要的科学意义。

纳米沉淀依靠溶剂转换过程引发溶质过饱和成核与聚集，并从溶液中相分离形成纳米尺寸胶体，具有操作简单、可控性高、能耗低等特点。本项目以具有良好生物相容性、生物降解性和生物利用度的具有高电荷密度和高氢键强度的天然聚合物为研究底物，通过研究天然来源聚合物经溶剂与非溶剂快速转换触发纳米沉淀的过程和条件，精确绘制了聚合物/溶剂/非溶剂的纳米沉淀三相图，以相图为指导对天然来源聚合物的成核与聚集过程进行编程操控，使聚合物可有序聚集于纳米粒/溶液相界面，形成核壳结构的仿生纳米胶囊。该方法可对天然来源聚合物仿生纳米胶囊的尺寸、表面功能、胶体稳定性等参数进行定制。根据参与聚合物的数量和种类，本项目可制备单组分单层纳米胶囊、多组分共混单层纳米胶囊和多组分共混多层纳米胶囊。此外，本项目提出了天然来源聚合物的纳米沉淀新的触发方法，通过水溶液间的溶剂转换触发高电荷密度的聚合物过饱和成核与聚集于相界面，形成天然来源聚合物仿生纳米胶囊。其纳米胶囊的胶体性质可通过底物浓度、溶液性质和溶剂转换过程进行调控。该水溶液纳米沉淀方法可避免了有机溶剂的使用，大大降低了制备过程中有机溶剂过量使用对环境和健康的风险，显著提高了纳米材料向应用转化的潜力。本项目对所制备的聚合物仿生的纳米胶囊的生物医药应用潜力进行了评估。项目的实施从理论上为纳米沉淀制备复杂形貌的多功能纳米材料提供了依据、从技术上为纳米沉淀编程操控分子有序组装奠定了基础，从应用上为可生物医用纳米材料的开发提供了新方法和新思路。