针对传统自降解分子合成策略模块化合成困难、偶合效率低下的局限性，本申请项目聚焦于“点击-自降解”反应的创新设计与复杂拓扑自降解高分子的合成应用，并拓展它们在本体微相分离材料与药物输运载体的功能应用。采用经典的1,5-点击反应、硫酰氟介导的交换反应、Suzuki反应等“点击”反应，优化构筑基元，筛选产物具有自降解特征的“点击”反应，即“点击-自降解”反应；基于“点击-自降解”反应设计合成涵盖了嵌段、线型-超支化嵌段、杂臂星型、刷状、环状等多种拓扑结构的全可降解自降解聚合物，阐明拓扑结构对本体/溶液组装体解聚速率与响应灵敏性的影响；整合“点击-自降解”反应创制可控链式缩聚，制备结构规整的自降解均聚物与嵌段共聚物，结构规整的自降解聚合物形成的组装体/本体相分离体系将用于药物纳米载体与纳米图案化检测诊断表面。该项目的实施将丰富触发式自降解高分子的拓扑结构与类别，为设计新一代智能纳米载体提供参考。

For conventional synthetic strategies of self-immolative molecules, especially for polymers, there always exist major concerns such as insufficient modular design, tedious synthesis, and inefficient coupling. To solve the above issues, in this proposal we focus on the design and synthesis of novel self-immolative polymers (SIPs) with complex architectures by means of “Click-to-Self-Immolate” reactions and their functional applications as drug delivery nanocarriers and “nano-patterned” surfaces. By utilizing conventional “Click” reactions such as 1,5-Click reactions, Sulfur(VI) Fluoride Exchange (SuFEx) reactions, and Suzuki Coupling reactions and optimizing appropriate building units, we are committed to screen novel “Click” reactions that can efficiently construct “clicked conjugates” possessing unique self-immolative feature, which are termed as “Click-to-Self-Immolate” reactions. Based on “Click-to-Self-Immolate” reactions, we attempt to design and synthesize SIPs with a series of chain topological structures, such as block, linear-hyperbranched block, miktoarm star, brush, and macrocyclic copolymers. Specifically, we plan to elucidate the effect of chain topological structures on the depolymerization rates and sensitivities of self-assemblies formed by SIPs in solution or bulk. “Living”/controlled polymerization will be integrated with “Click-to-Self-Immolate” reactions to implement chain-growth Suzuki polycondensation with the formation of self-immolative homopolymers and block copolymers with narrow molecular weight distributions. Furthermore, assemblies and microphase separation systems fabricated from well-defined SIPs will be applied as drug delivery nanocarriers and “nano-patterned” surfaces for clinical diagnosis and detection. The accomplishment of the above proposed research contents is expected to enrich the topological structures and categories of self-immolative polymers, as well as to provide an important reference for the construction of next-generation smart nanocarriers and sensitive detection and diagnostic systems.