基于金属-儿茶酚配位作用的环境响应性聚合物纳米凝胶用作药物载体

Metal-catechol coordination shows great potential in the fabrication of environmental-responsive nano carriers for controlled drug release because of their desirable properties, such as fast response, controllability, and diverse chelation ability. This project intends to explore the preparation of stimuli-responsive nanogels based on metal-catecholate complexes and their application as drug carriers. A new type of pH-responsive nanogels are synthesized using metal-catecholate complexes as a crosslinker, and the pH-responsive degradability and controlled drug release behavior of the nanogels are investigated. The influence of initiator, solvents, and synthesis process on free radical polymerization in the presence of metal-catecholate complexes are systematically studied, to find out suitable polymerization approach for preparing metal-catecholate complexes bonded nanogels. The effect of the metal-catechol coordination crosslinker on stimuli responsibility and bio-imaging ability of nanogels are further demonstrated, as guide to develop a full-featured (environmental response and bio-imaging) nano drug carriers for the integration of diagnosis and therapy.

金属离子与儿茶酚的配位作用具有响应快、可调控、配体选择范围广等特点，且这种配位作用在特定条件下对外界刺激的响应还具有可逆性，可用于发展新型环境响应性药物控释载体。本项目拟探索含有金属-儿茶酚配位键的聚合物纳米凝胶的制备及作为抗肿瘤药物载体的应用。以三价铁离子与儿茶酚的配合物为交联剂，制备聚合物纳米凝胶，并研究其pH响应降解行为及作为药物载体时的可控释药行为。系统研究引发剂、溶剂、聚合方式等因素对金属-儿茶酚配位键存在下的自由基聚合的影响，在此基础上探索适合制备含金属-儿茶酚配位键的纳米凝胶的聚合引发体系。评价金属-儿茶酚配位交联点的结构及配比对聚合物纳米凝胶环境响应性能及生物成像性能的影响，并以此为指导发展出具有全功能(pH响应降解和生物成像)的诊疗一体化纳米凝胶载药系统。

金属离子与儿茶酚的配位作用因其响应快、可调控、配体选择范围广等优点，在设计制备新型环境响应性药物控释载体方面备受关注。本项目探索了含有金属-儿茶酚配位键的聚合物纳米凝胶的制备及作为抗肿瘤药物载体的应用。通过蒸馏沉淀聚合和水相沉淀聚合两种方法制备了一系列环境响应性可降解聚合物纳米凝胶，研究表明制备的纳米凝胶均具有灵敏的环境响应可降解性，作为药物载体可实现肿瘤环境条件下的可控释药，并实现对肿瘤细胞的高效杀伤。本项目的成功实施不仅促进了含金属-儿茶酚配位键的纳米凝胶的发展，也系统探索了多种聚合方法在制备可降解聚合物纳米凝胶中的应用，为后续开发多功能诊疗一体化纳米凝胶载药系统打下了基础。在本项目的支持下，共发表论文5篇，申请发明专利3项。