以酰胺键的变化为生物可降解聚合物植入多重温敏相转变

Complex tailored polymers with multiple transitions between soluble and insoluble states have been designed and studied not only for better understanding of the structural effects on phase transitions, but also to enable innovative approaches to nanoparticle self-assembly, cancer therapy, regenerative medicine and protein purification. The project is intended to regulate hydrogen(H) bonding interactions by varying pendant amide groups, implanting thermo-responsive multi-phase transitions into biodegradable polymers (poly-ε-caprolactone and peptoid) without any H bond donor. It is emphasized that how molecular weight and pendant groups will influence LCST (or UCST). The effect of crystallinity, hydrophilicity/hydrophobicity and flexibility of the main chain on the product property will be studied. The pattern among structural changes of main chain and side groups, intra/inter molecular H bonding interactions and thermo-sensitive phase transition behavior will be revealed. A theoretical guidance is going to be provided for molecular design of biodegradable polymers with thermo-responsibility. Further study is to prepare block copolymers with both optimized LCST and UCST type segments. The self-assembly behavior in the dilute solution and sol-gel transition in the concentrated state of the block copolymers will be demonstrated with varied temperatures, exploring as smart materials for potential biomedical applications. Implementation of the project will promote temperature-sensitive biodegradable polymers with multi-phase transitions as the development of smart materials and widen their application in the biomedical field.

设计和研究复杂聚合物体系在可溶态和不溶态之间的多重变化，不仅能更好的理解分子结构对相转变行为的影响，还能为纳米颗粒自组装、肿瘤治疗、再生医学、蛋白质提纯等领域提供创新方案。本项目拟以侧酰胺基的变化调节氢键互相作用，为缺乏氢键给体的生物可降解聚合物主链（聚己內酯和类肽）植入多重温敏相转变，着重研究分子量和侧基种类对聚合物LCST（或UCST）的调控，考察主链结晶性、亲疏水性和柔顺性对产物性能的影响，揭示主链和侧基结构变化与分子内／间氢键作用、温敏相转变行为之间的影响规律，为可降解温敏聚合物材料的设计提供理论指导；进一步选择最优化体系制备同时具有LCST和UCST型相转变的嵌段共聚物，研究变温时稀溶液的自组装行为和浓溶液的凝胶－溶胶转变行为，探索其作为生物医用智能材料的潜在应用。该项目的实施将促进可降解多重相转变温敏聚合物作为智能材料的发展，并推动其在生物医药领域的广泛应用。

实现酰胺键调节的温敏性可降解聚合物制备，不仅能加深酰胺键对氢键形成和相转变影响的理解，指导温敏性聚合物的合成；还能发展可降解的刺激响应性材料，为制备智能纳米颗粒/水凝胶提供创新方案。本项目以聚己内酯和聚类肽为基体，将酰胺基团分别引入此类可降解聚合物中，实现了聚己内酯主链上侧酰胺基的变化对LCST和UCST型相转变的调节，揭示了侧酰胺结构变化与分子间氢键作用、温敏相转变行为之间的构效关系；而缺乏氢键的聚类肽主链强亲水性限制了其在水溶液中产生温敏性相转变，引入聚肽组分与类肽共聚，可方便调节共聚物的水溶性，发现了不同序列结构对共聚物水溶性的影响规律，实现了共聚物浓度依赖的溶胶-凝胶转变；最后选择最优化的聚己内酯体系，实现了对温敏性材料相转变温度的一系列调控，并研究了变温下的溶液中聚集体变化行为，探索了这类材料作为药物和蛋白载体的应用，对推动智能生物医用材料发展具有重要意义。