目的 利用多巴胺堿性條件下自組裝成聚合法制備葉酸（FA）靶向的紫杉醇（PTX）納米粒（NPs），并對其進(jìn)行表征，探究體外抗宮頸癌效果。方法 采用反溶劑沉淀法聯(lián)合高壓均質(zhì)制備PTX-PEG₂₀₀₀PCL₂₀₀₀ NPs，將鹽酸多巴胺置于堿性條件下，其在NPs的表面氧化自聚合形成聚多巴胺（PDA）薄層，隨后將FA對其表面修飾，得到PTX-PDA-FA NPs。利用動(dòng)態(tài)光散射法、透射電鏡法考察NPs的粒徑及形態(tài)，高效液相法測定PTX含量，考察NPs的穩(wěn)定性、溶血性、體外釋放等表征、用MTT法評價(jià)NPs對HeLa細(xì)胞的細(xì)胞毒作用。結(jié)果 成功制得PTX-PDA-FANPs，粒徑（182.9±3.921）nm，分散指數(shù)（PDI）值為0.113±0.026，Zeta電位為-29.2 mV，透射電鏡下呈棒狀。NPs在5%葡萄糖、血漿中基本穩(wěn)定；無溶血現(xiàn)象；在體外持續(xù)緩慢釋放。MTT結(jié)果顯示，與無FA靶向的NPs比較，PTX-PDA-FA NPs對HeLa細(xì)胞表現(xiàn)出更高的抑制率。結(jié)論 利用PDA法表面功能化是一種更加安全快捷的制備靶向NPs的方法，能夠更好的實(shí)現(xiàn)增效減毒，是非常有潛力的納米給藥系統(tǒng)。

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

國家自然科學(xué)基金委-廣東省聯(lián)合基金（U1401223）