目的 利用多巴胺碱性条件下自组装成聚合法制备叶酸（FA）靶向的紫杉醇（PTX）纳米粒（NPs），并对其进行表征，探究体外抗宫颈癌效果。方法 采用反溶剂沉淀法联合高压均质制备PTX-PEG₂₀₀₀PCL₂₀₀₀ NPs，将盐酸多巴胺置于碱性条件下，其在NPs的表面氧化自聚合形成聚多巴胺（PDA）薄层，随后将FA对其表面修饰，得到PTX-PDA-FA NPs。利用动态光散射法、透射电镜法考察NPs的粒径及形态，高效液相法测定PTX含量，考察NPs的稳定性、溶血性、体外释放等表征、用MTT法评价NPs对HeLa细胞的细胞毒作用。结果 成功制得PTX-PDA-FANPs，粒径（182.9±3.921）nm，分散指数（PDI）值为0.113±0.026，Zeta电位为-29.2 mV，透射电镜下呈棒状。NPs在5%葡萄糖、血浆中基本稳定；无溶血现象；在体外持续缓慢释放。MTT结果显示，与无FA靶向的NPs比较，PTX-PDA-FA NPs对HeLa细胞表现出更高的抑制率。结论 利用PDA法表面功能化是一种更加安全快捷的制备靶向NPs的方法，能够更好的实现增效减毒，是非常有潜力的纳米给药系统。

Objective Folate-targeted paclitaxel (PTX) nanoparticles were prepared by self-assembly polymerization under dopaminealkaline conditions and characterized to investigate the anti-cervical cancer effect in vitro. Methods PTX-PEG₂₀₀₀PCL₂₀₀₀ nanoparticles were prepared by anti-solvent precipitation combined with high-pressure homogenization. By dopaminepolymerization method, dopamine-hydrochloride was placed under alkaline conditions to oxidize and self-polymerize on the surface of the nanoparticles to form PDA thin layer, and then the surface was modified with folic acid (FA) to obtain PTX-PDA-FA NPs. Nanoparticles size and morphology was measured by dynamic light scattering (DLS) and transmission electron microscopy (SEM). Drug content was determined by high performance liquid chromatography (HPLC). The stability of the nanoparticles, hemolytic, in vitro release were characterized and cytotoxic effect against HeLa was examined by MTT assay. Results PTX-PDA-FA NPs were successfully prepared,with particle size of 182.9±3.921 nm, dispersion index (PDI) value of 0.113±0.026 and Zeta potential of -29.2 mV. It was stable in 5% glucose and plasma. There was no hemolysis and showed sustained slow release in vitro. MTT results showed that PTX-PDA-FA nanoparticles showed a higher inhibition rate on HeLa cells compared with folate-free nanoparticles. Conclusion Surface functionalization by polydopamine method is a safer and faster way to prepare targeted nanoparticles, which can better enhance the efficacy and reduce toxicity, and is a promising nano-drug delivery system.

R965

国家自然科学基金委-广东省联合基金（U1401223）