目的 制备一种通过叶酸受体途径作用于肿瘤细胞的叶酸修饰水飞蓟宾固体脂质纳米粒（FA-SIL-SLN），考察FA-SIL-SLN对A549细胞抑制作用。方法 酰化反应合成膜材（FA-PEG₃₃₅₀-DSPE），采用乳化-超声分散法制备FA-SIL-SLN，并研究其理化性质。MTT法测定FA-SIL-SLN对A549细胞的抑制率；流式细胞分析仪分析其对细胞周期的影响。结果 合成了膜材FA-PEG₃₃₅₀-DSPE；制备的FA-SIL-SLN外观圆整、平均粒径为（103±21）nm，包封率为（90.73±0.33）%、载药量为（2.13±0.17）%，体外释药实验表明其具有良好的缓释特性；对A549细胞的抑制作用呈现明显的量效和时效关系；阻滞细胞增殖。结论 本实验为叶酸介导的抗肿瘤给药系统研究提供了依据。

Abstract: Objective To prepare silybin solid lipid nanoparticle modified by folic acid (FA-SIL-SLN) and to investigate its inhibitory effect on non-small cell lung cancer A549 cells. Methods The compounding membrane material FA-PEG₃₃₅₀-DSPE was synthesized by acylation; FA-SIL-SLN was prepared by emulsion-ultrasonic dispersion method; The physicochemical properties were studied; The inhibitory rate on A549 cells was determined by MTT method; The effect on cell cycle was analyzed by flow cytometry. Results The membrane material FA-PEG₃₃₅₀-DSPE was synthesized. The prepared FA-SIL-SLN was round and even, the average partical size was (103 ± 21) nm, the encapsulation efficiency was (90.73 ± 0.33)%, and the drug loading was (2.13 ± 0.17)%. The in vitro release experiments showed that it had good sustained-release characteristics and blocked cell proliferation, and the inhibitory effect on A549 cells presented the obvious dose-effect and time-effect relationships. Conclusion This study provides a basis for the research on folate-mediated antitumor drug delivery systems.

黑龙江省教育厅重点项目（12511z027）