氨基酸类聚膦腈纳米材料的合成与机理研究

Phosphazene has been considered as the most important class of inorganic-organic polymers since the commercialization of the silicones. However, the harsh polymerization process restricts its commercial application. Recently, a new polycondensation reaction for the synthesis of highly cross-linked polyphosphazene was proposed. The mild reaction conditions and simple post-treatment of the polycondesation process open a new door for the practical application of polyphosphazene. In the biomedical field, linear polyphosphazenes with amino acid side chains are the most attractive material, which not only has excellent biocompatibility, controllable biodegradation, non-toxic degradation products, and the mechanical properties can be adjusted in a wide range. Therefore, they have shown great potential in the field of tissue engineering, drug delivery and artificial blood vessels at so on. Whether amino acid also can carry out polycondensation reaction with hexachlorocyclotriphosphazene and form highly cross-linked polyphosphazene with a variety of nanostrcutures, not only challenges the habitual thinking that the formation of cross-linked polyphosphazene nanostructures requires rigid monomers, and a new class of nanostructured biomaterials may be developed. In this project, we will focus on the polycondensaztion reaction between amino acid and hexachlorocyclotriphosphazene, and investigate the formation and evolution rule of nanostructures during polymerization on flexible monomer, the relationship between amino acid structures and properties of materials, the biodegradation pathways of amino acid containing cross-linked polyphosphazene and biological safety of degradation products. We also further study the approaches to build a variety of nano core-shell structures using amino acid containing cross-linked polyphosphazene and other functional units, and explore their applications in bioapplication.

聚膦腈是继有机硅材料后，又一类很有前途的无机-有机杂化高分子。但苛刻的聚合工艺一直制约着其商业化应用。最近发明的缩聚反应合成环交联聚膦腈的方法，不仅反应条件温和，且可形成丰富的纳米结构，因此为聚膦腈的实用化打开了新的大门。在生物医学领域，最受关注的是带有氨基酸侧链的线性聚膦腈，它不仅具有优良的生物相容性、生物降解可控性、降解产物无毒性，且机械性能在宽范围内可调。能否将氨基酸单体借鉴到环交联聚膦腈的缩聚反应中，制备具有纳米结构的环交联聚膦腈，不仅突破环交联聚膦腈需要芳香单体的习惯思维，而且可能发展出一类全新纳米结构生物材料。本项目针对氨基酸和六氯环三膦腈的缩聚反应，研究脂肪族反应单体缩聚反应中纳米结构的形成和演化规律，环交联聚膦腈材料的结构与性能关系，聚膦腈生物降解途径和降解产物安全性，氨基酸环交联聚膦腈与其他功能单元构筑纳米核壳结构，探索其生物医学领域的应用。

环交联聚磷腈具有合成简单、易生物降解等优点，但是以往环交联聚磷腈的合成均使用芳香单体，限制了该材料的生物医学应用。本项目探索采用非芳香性单体合成环交联聚磷腈的可行性，研究其聚合反应机理、探讨其在生物医学领域的应用。本项目执行期间: (1)我们发展了氨基酸环交联聚磷腈纳米材料的制备方法，提出“水刺激自组装沉淀共聚法的反应机制，这个机理的发现为非芳香环交联聚磷腈的制备提供了理论基础; (2) 在此基础上,我们构建了易于合成的聚磷腈自框架给药系统（DSFDSs)，这种送药体系具有高载药率、循环稳定性好、对肿瘤组织具有很好的抑制效果，且对主要器官毒性低，是一种非常优秀的送药平台。我们还发展了抗耐药性的双药自输送体系以及热疗-化疗联合治疗的自框架送药体系; (3) 基于聚磷腈的自框架的概念，发展了一类兼具物理反射和化学吸收特征的UV全谱抗紫外自框架纳米材料，经过动物实验证明该材料具有优秀的生物安全性，其防紫外效果达到商业化TiO2的水平，有望成为下一代防晒霜的紫外屏蔽剂。