项目名称： 超支化触发式自降解聚合物的设计合成与功能构筑

项目编号： No.21504087

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 刘固寰

作者单位： 中国科学技术大学

项目金额： 22万元

中文摘要： 针对线型或树枝状触发式自降解聚合物不能兼具信号化学放大和简便合成双重优势的局限性，本申请项目聚焦于触发式自降解超支化聚合物(hSIP)的创新设计与合成，并拓展他们在药物输运载体和超灵敏检测诊断方面的功能应用。采用经典的一锅法缩聚与后修饰策略，优化和筛选构筑基元，设计合成涵盖了多类支化基元、触发基元，以及生物活性报告基元和外围靶向基元的hSIP；拟在hSIP骨架外周通过自降解连接基共价键合前药分子和利用荷电hSIP与生物大分子的静电络合，程序化调控细胞或特征病变组织微环境触发的原药及生物大分子释放；将hSIP固有的化学放大效应与酶促反应相结合，构建正反馈循环放大体系以实现灵敏检测；以此为基础进一步集成hSIP与酶联免疫吸附检测等技术，力图发展用于临床超灵敏检测诊断的新策略。该项目的实施预期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与超灵敏检测诊断功能体系提供重要参考。

中文关键词： 触发式自降解聚合物；超支化聚合物；纳米药物载体；灵敏检测；信号放大

英文摘要： For conventional dendritic or linear self-immolative polymers, there always exists a major concern that it is not possible to simutaneously combine two key advantages, i.e., facile synthesis and signal amplification capability. To solve the above issue, in this proposal we focus on innovating the design and synthesis of Hyperbranched Self-Immolative Polymers (hSIPs) and their functional applications as drug delivery nanocarriers and ultrasensitive detection and diagnostic systems. By utilizing conventional strategies combining one-pot polycondensation and post-modification, optimizing and screening appropriate building units, we attempt to design and synthesize a series of hSIPs with varying responsive mechanisms and functions through the integration of three types of branching units, four types of triggering entities, and a variety of bioactive reporter residues and targeting moieties. Specifically, we plan to functionalize the periphery of hSIPs with prodrugs via self-immolative linkers and fabricate polyion complexes via reversiable electrostatic interactions between charged hSIPs and biomacromolecules of interest, aiming to achieve programmed release of drugs and biomacromolecles triggered by intracellular or pathological milieu. Specific enzymatic reactions will combined with the intrinsic signal amplification capability of hSIPs to construct positive feedback amplification systems for ultrasensitive detection. Furthermore, we will integrate these positive feedback amplification systems with clinically relevant techniques such as enzyme-linked immunosorbent assay (ELISA) to explore their potential applications in clinical diagnosis and detection. The accomplishment of the above proposed research contents is expected to enrich 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 ultrasensitive detection and diagnostic systems.

英文关键词： Self-Immolative Polymer;Hyperbranched Polymer;Drug Delivery Nanocarries;Sensitive Detection;Signal Amplification