苯硼酸酯类氧化敏感高分子及高分子前药的合成、性质

Reactive oxygen species (ROS) play key roles in many physiological processes such as cell signaling and host innate immunity. However, once they are overproduced, ROS may damage biomolecules in vivo and cause diseases such as cardiovascular or neurodegenerative diseases, cancer, and so forth. Oxidative stress is usually implicated in various inflammatory tissues, representing an important target for the development of various therapeutic strategies. Therefore, various probes for in vitro detection of ROS or in vivo diagnosis of the oxidative stress-relevant diseases have been developed. Oxidation-responsive polymers have also attracted great interest because of their potential applications in biomedical fields and have advanced significantly in the past decade. However, the oxidation-responsive polymers are still far away from real applications as biomaterials due to their inefficient sensitivity to in vivo concentration of ROS, non-degradability, complicated synthesis, etc. In this project, we will focus on the oxidation-responsive polymers composed of phenylboronic ester units with self-immolative feature. We will design and synthesize a family of H2O2-responsive, degradable polymers with different topology by using Passerini multi-component reaction; and systematically investigate the relationship between structure and various properties of the polymers. In addition, biodegradable polyesters with pendent phenylboronic ester and a new type of oxidation-responsive polymeric prodrugs will also be developed.

活性氧物质浓度偏高（Oxidative stress）是炎症部位、部分恶性肿瘤组织的生物学特征之一，可作为纳米药物或诊断试剂的靶标。尽管氧化敏感类高分子近十年来得到了长足发展，但仍存在氧化敏感度较低、合成复杂、结构可控性不佳等问题。利用简便的合成方法制备生物相容性好、降解速率和热/力学性质易调的氧化敏感高分子对于发展适用于不同要求的氧化敏感载体材料有较大意义。本项目拟以具有自分解结构特征的苯硼酸（酯）为核心基元，设计合成一系列拓扑结构不同、对H2O2敏感的降解性聚合物或氧化敏感高分子前药，详细研究其结构-性质间的关系规律，建立新型氧化敏感高分子材料体系平台，为进一步实现氧化敏感高分子载药体系在恶性肿瘤组织或炎症部位定位给药这一目标奠定基础。

活性氧物质浓度偏高（Oxidative stress）是炎症、部分恶性肿瘤组织的生物学特征之一，可作为纳米药物或诊断试剂的靶标。利用简便的合成方法制备生物相容性好、降解速率易调的氧化响应高分子对于发展适用于不同要求的氧化敏感载体材料有较大意义。本项目以具有自分解结构特征的苯硼酸/酯为核心基元，采用环状单体开环聚合、Passerini多组分反应、自由基聚合等方法，设计合成了多种结构不同、对H2O2敏感的可降解聚合物或氧化响应高分子前药，详细研究了其结构-性质之间的关系规律，建立了新型氧化响应高分子材料的合成平台，初步证实了这类基于苯硼酸酯基元的氧化响应高分子材料可用于恶性肿瘤组织、炎症部位的定位给药及葡萄糖响应胰岛素给药体系。此外，通过环状单体的开环聚合，还制备了侧基含氧族元素（S/Se/Te醚）的聚己内酯及聚碳酸酯类氧化响应聚合物，阐明了它们作为光动力治疗纳米药物载体的可行性。