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目的 本文采用反相微乳法构建叶酸修饰的亚砷酸钙脂质体“靶-控”递药系统(FA-LP-CaAs)以减小三氧化二砷(ATO)的毒副作用,为原发性肝癌的治疗提供新思路.方法 采用Malvern粒径仪和透射电镜考察其粒径、分布、Zeta电位和形态;电感耦合等离子发射光谱法考察载药量、包封率及体外释放情况;噻唑蓝法(MTT)考察其对HepG2和LO2细胞的毒性并研究对HepG2细胞周期及细胞凋亡的影响;采用激光共聚焦和流式细胞仪考察细胞对递药系统的摄取;构建小鼠肝癌模型,采用活体荧光考察药物在体内的分布.监测给药后ATO在组织中的分布情况、肿瘤体积及体重变化,并对肿瘤进行HE染色,评价FA-LP-CaAs的肝癌靶向性以及体内抗肿瘤效果.结果 FA-LP-CaAs粒径、电位、PDI分别为(122.67±2.18)nm,(12.81±0.75)mV、0.22±0.01,具有明显的“核-壳”结构.FA-LP-CaAs的载药量为18.49％ ±1.14％.体外实验结果表明,FA-LP-CaAs对HepG2细胞有较强的杀伤作用,能够提高细胞摄取能力.体内实验结果表明,FA-LP-CaAs能够显著增加ATO在肿瘤部位的分布,抑制肿瘤生长.结论 本文成功构建了外观圆整,粒径均一,多分散系数良好,“核-壳”结构明显,具有较高载药量和pH响应、肿瘤靶向递药以及药物缓释等特性的FA-LP-CaAs,丰富了ATO在抗肝癌方面的研究与应用,为肝癌的治疗提供了新方法.“,”Objective To reduce the toxicity and side effects of arsenic trioxide (ATO) and provide a new approach for the treatment of primary liver cancer, a folic acid-modified calcium arsenite liposomal “target-controlled” drug delivery system (FA-LP-CaAs) was fabricated using the reverse microemulsion method. Methods A Malvern particle size analyzer and a transmission electron microscope were employed to determine the particle size, distribution, zeta potential and morphology of FA-LP-CaAs. Further, inductively coupled plasma emission spectrometry was employed to determine the drug loading capacity, entrapment efficiency, and in vitro release behavior of FA-LP-CaAs. To determine its toxicity in human hepatoma cells (HepG2) and human normal hepatocytes (LO2) and its effect on HepG2 cell cycle and apoptosis, the MTT method was used. Laser confocal and flow cytometry were also employed to determine the uptake of FA-LP-CaAs by cells. After establishing a mouse liver cancer model, the in vivo distribution of the drug included in the formulation was investigated using in vivo fluorescence. To evaluate the liver cancer targeting and anti-tumor effects of FA-LP-CaAs in vivo, the distribution of ATO in tissues and changes in tumor volume and body weight after liposomal administration were investigated using hematoxylin-eosin (HE)-stained tumor sections. Results The particle size, zeta potential and PDI of FA-LP-CaAs were (122.67 ± 2.18) nm, (12.81 ± 0.75) mV and 0.22 ± 0.01, respectively, while its drug loading capacity was 18.49％ ± 1.14％. In vitro experimental results revealed that FA-LP-CaAs had a strong killing effect on HepG2 cells. Further, the cell uptake capacity of this formulation was found to improve. Based on in vivo assessments, FA-LP-CaAs could significantly increase the distribution of ATO in tumor sites and inhibit tumor growth.Conclusions Herein, an FA-LP-CaAs formulation was successfully fabricated. This liposomal drug delivery system had a round appearance, uniform particle size, good polydispersity coeffi-cient, evident “core-shell” structure, high drug loading capacity and pH response, tumor targeted drug delivery and sustained drug release. These findings support further research and the application of ATO as an anti-liver cancer prodrug and provide a new method for the treatment of liver cancer.