自组装聚合物囊泡具有亲水内腔和疏水膜的类脂质体结构，适合装载水溶性化疗药物进行肿瘤靶向治疗，但是目前报道的聚合物囊泡普遍存在递送过程中药物过早释放导致药效降低及毒副作用增大的问题。为此，本项目拟通过分子设计合成含叔胺基团的两亲性接枝聚膦腈，在自组装形成纳米囊泡并装载水溶性化疗药物（如盐酸阿霉素）的同时，利用叔胺直接作用或与强还原剂协同作用，还原氯金酸原位生成纳米金，形成均匀杂化交联网络，增加囊泡疏水膜致密性，从而抑制所包载的水溶性化疗药物在血液循环中的过早释放，显著提高药物的递送稳定性。采用多种表征手段，探讨载体与纳米金的杂化机理，阐明聚膦腈化学结构、纳米金杂化条件对杂化囊泡构成及理化性能的影响；并通过药动及体内外药效学评价，筛选聚合物结构及杂化条件，最终获得稳定递送药物并兼具高效载药、肿瘤靶向、响应性释药等多种功能的纳米金杂化聚合物囊泡，为肿瘤治疗纳米递送系统性能的完善提供重要的新策略。

Polymersomes are a class of artificial vesicles self-assembled by amphiphilic polymers. Recently, polymersomes have attracted growing interest for cancer therapy since their structure is analogous to that of liposomes containing hydrophilic chambers for loading water-soluble substances. However, the premature drug release from polymersomes in blood circulation system frequently occurs, which results in increased systemic side effects and decrease anti-cancer efficacy. With the aim to overcome this problem, we will construct polyphosphazene-gold nanoparticle hybrid vesicle with multifunctions to load water-soluble chemotherapeutics, such as doxorubicin hydrochloride. By taking advantage of the reduction activity of tert-amino group in polyphosphazene towards tetrachloroauric acid with or without NaHB4 , gold nanopartiles can grow in situ to make the hydrophobic member of polymersomes more denser as crosslinkers. Therefore, the premature drug release during blood circulation can be effectively inhibited, and the improved anti-cancer efficacy and reduced side effects will be expected. In this research, the hybrid mechanism of polyphosphazene-gold nanoparticle will be fully investigated by various experimental methods. And the relationship among polymer chemical structure, preparation conditions of hybrid vesicles and the physicochemical properties of hybrid vesicles will be clarified. Followed by pharmacokinetics and pharmacodynamics studies, some optimized polymers as drug carriers and preparation method of hybrid vesicles will be finally obtained, which makes the hybrid vesicles have comprehensive excellent properties of stability during circulation, drug loading capability, tumor targeting, pH-sensitive drug release in tumor. This project will contribute some new ideas and experimental evidence to how to construct ideal nanoparticles for water-soluble drug via self-assembled polymers.