开环聚合诱导自组装制备生物可降解嵌段共聚物胶束

Recently polymerization-induced self-assembly (PISA) has been demonstrated to be a robust and efficient route for in situ preparation of diblock copolymer nanoparticles at high concentrations. This technique is based on the controlled/living radical polymerization and thus only vinyl monomers are applied in PISA. Therefore, the main chain of core-forming block prepared via PISA process is carbon-carbon backbone, resulting in a difficulty in introduction of functional groups into the chain and a general lack of biodegradability. Herein, in this research we first employ ring-opening polymerization for PISA synthesis and develop a new strategy for efficient preparation of main-chain-functionalized and biodegradable block copolymer nanoparticles. (S)-Benzyl 3-(2,5-dioxooxazolidin-4-yl)propanoate, ε-caprolactone and α-allyl-ε-caprolactone will be used as representative core-forming monomers. Poly(g-benzyl l-glutamate), poly(ε-caprolactone) and poly( α-allyl-ε-caprolactone) block copolymer nanoparticles can be one pot prepared via combination of dispersion polymerization and PISA in selected solvents using corresponding core-forming monomers. Influences of the chain length of core-forming block, temperature and concentration on the self-assembly of diblock copolymer will be studied for better control of the nanoparticle morphology. This research on ring-opening polymerization-induced self-assembly opens a new avenue for efficient preparation of biodegradable block copolymer nanoparticles and is important for the future development of PISA technique.

聚合诱导自组装是近几年发展起来的一种简单、高效制备嵌段共聚物胶束的重要技术, 但目前该技术都是基于活性/可控自由基聚合，仅适用于烯烃类成核单体，制备的成核嵌段主链为碳-碳骨架，难以实现主链的功能化，同时也缺乏生物降解性。为此，本申请项目首次将开环聚合应用于聚合诱导自组装技术，提出一种高效制备核嵌段主链功能化、生物可降解嵌段共聚物胶束的新方法。以5-苄酯N-羧基环内酸酐、ε-己内酯和α-烯丙基-ε-己内酯分别作为代表性成核单体，在选择性溶剂中进行分散聚合，通过诱导自组装分别制备聚谷氨酸苄酯、聚ε-己内酯和聚α-烯丙基-ε-己内酯的嵌段共聚物胶束。研究浓度、成核嵌段的长度等因素对自组装体形貌的影响，实现对胶束形貌的调控。通过对开环聚合诱导自组装的研究，发展一条规模化制备生物可降解嵌段共聚物胶束的新途径，推动这类胶束走向实际应用，同时为聚合诱导自组装技术的发展提供新的思路。

聚合诱导自组装是近些年快速发展起来的一种可用于高效制备嵌段共聚物纳米胶束的技术，但目前该技术主要基于活性自由基聚合，得到的聚合物胶束降解性差。开环聚合是合成生物可降解高分子的一种重要方法，研究开环聚合诱导自组装技术，不仅具有重要的理论意义，同时对于高效合成可降解嵌段共聚物纳米胶束具有重要的应用价值。本项目通过以5-苄酯N-羧基环内酸酐（BLG-NCA）为核单体，以甲氧基聚乙二醇胺作为稳定嵌段，在选择性溶剂中进行开环分散聚合，通过调节成核嵌段的长度，制备了球、纤维状的纳米胶束，还研究了反应温度、溶剂种类等对聚合反应控制性的影响。此外还设计合成了苯基甲基乙交酯（MPD）作为成核单体，以甲氧基聚乙二醇为稳定嵌段进行开环分散聚合，得到条状结构的自组装体，并研究了不同催化剂对其聚合反应的影响。本项目将首次开环聚合技术应用到聚合诱导自组装领域制备主链可降解的聚合物胶束，并揭示了在聚合反应过程中的问题，具有重要的理论意义。