目的 制備一種通過葉酸受體途徑作用于腫瘤細(xì)胞的葉酸修飾水飛薊賓固體脂質(zhì)納米粒（FA-SIL-SLN），考察FA-SIL-SLN對A549細(xì)胞抑制作用。方法 酰化反應(yīng)合成膜材（FA-PEG₃₃₅₀-DSPE），采用乳化-超聲分散法制備FA-SIL-SLN，并研究其理化性質(zhì)。MTT法測定FA-SIL-SLN對A549細(xì)胞的抑制率；流式細(xì)胞分析儀分析其對細(xì)胞周期的影響。結(jié)果 合成了膜材FA-PEG₃₃₅₀-DSPE；制備的FA-SIL-SLN外觀圓整、平均粒徑為（103±21）nm，包封率為（90.73±0.33）%、載藥量為（2.13±0.17）%，體外釋藥實(shí)驗(yàn)表明其具有良好的緩釋特性；對A549細(xì)胞的抑制作用呈現(xiàn)明顯的量效和時(shí)效關(guān)系；阻滯細(xì)胞增殖。結(jié)論 本實(shí)驗(yàn)為葉酸介導(dǎo)的抗腫瘤給藥系統(tǒng)研究提供了依據(jù)。

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.

黑龍江省教育廳重點(diǎn)項(xiàng)目（12511z027）