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以透明质酸(HA)及硝基咪唑(NI)衍生物为原料,通过酰胺反应合成了一种两亲性接枝聚合物(HA-NI).该聚合物具有缺氧响应性和肿瘤靶向性.利用傅里叶红外光谱(FT-IR)和核磁共振(NMR)对接枝聚合物的结构进行了表征,同时基于1H NMR计算出接枝聚合物中NI的取代度.HA-NI在水中自组装形成胶束,利用动态光散射仪(DLS)表征胶束大小并对胶束的稳定性进行了研究,利用原子力显微镜(AFM)和透射电镜(TEM)观察胶束形貌.载药胶束的载药率(DL)和包封率(EE)通过紫外-可见吸收光谱(UV)测试并计算得到.胶束的缺氧响应性利用DLS、AFM、TEM、UV等探究.实验证明,该聚合物胶束具有缺氧响应性并对药物表现出良好的控制释放能力,在常氧环境下,胶束稳定存在;而在缺氧环境下,胶束散开,药物快速且完全地释放.“,”Hypoxia is a hallmark of tumor.Based on this feature,a hypoxia-responsive drug delivery system combined with tumor-targeting was developed.HA-NI conjugates were prepared by grafting the carboxyl group of hyaluronic acid (HA) with an amine group of nitroimidazole (NI) derivative in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS).The structure of HA-NI conjugates was confirmed by FT-IR and 1H NMR,the degree of substitution (DS) of NI derivative was also calculated based on 1H NMR.Amphiphilic HA-NI conjugates could self-assemble into micelles by ultrasonic method.The size and morphology of micelles were characterized by dynamic light scattering (DLS),atomic force microscope (AFM) and transmission electron microscopy (TEM),the stability of micelles was also investigated by DLS.It was found the size of micelles was in the range of 80～220 nm while the DS decreased from 6.5％ to 3.6％.Doxorubicin (DOX) was encapsulated in micelles,and DOX-loaded micelles had smaller sizes compared with blank micelles.Drug-loading (DL) and entrapment efficiency (EE) were obtained by UV-Vis analysis and increased with the increasing DS.Under hypoxic condition,micelles became bigger and size distribution of micelles became wider,it was clear to observe the destruction of micelles by AFM and TEM.UV spectrum revealed the characteristic peak belonging to NI at 325 nm disappeared and Zeta potential increased from-30.6±0.4 mV to-24.9±0.5 mV 6 h later.In vitro drug release studies demonstrated that DOX was released from HA-NI micelles in a hypoxia-dependent manner:micelles were sufficiently stable at normoxic condition while accomplished a rapid drug release under hypoxic condition.