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目的:东莨菪亭(7-羟基-6甲氧基香豆素,化学式C10H8O4,简称HMC)是从常绿钩吻(Gelsemium sem pervirens)中提取的一种天然香豆素类化合物,被认为具有抗癌活性。本研究将HMC制成聚乳酸聚乙醇酸共聚物(polylactic-co-glycolic acid,PLGA)纳米颗粒胶囊,通过多项指标观察其与非纳米HMC相比,在被细胞摄取、生物利用度及对细胞凋亡的影响(抗癌活性)等方面是否有所提高。方法:人黑色素瘤A375细胞用来检测HMC及纳米HMC颗粒(nano-7-hydroxy-6-methoxy coumarin,NHMC)的被细胞摄取率及抗癌活性;通过动态光散射确定NHMC的颗粒大小、多分散性指数及电动电位;扫描电子显微镜及原子力显微镜检测纳米颗粒的表面形态。结果:HMC制成纳米颗粒胶囊的包封率超过85%。NHMC颗粒的平均直径小于110nm,其多分散性系数为0.237,提高了其被细胞摄取率及生物活性。NHMC被细胞摄取的时间(15min)明显少于非纳米HMC(30min)。测定细胞内某些信号分子mRNA的表达,表明NHMC作用细胞后能够下调细胞周期素D1(cyclin-D1)、增殖细胞核抗原(PCNA)、存活素(survivin)及信号转导和转录活化因子3(Stat-3)的表达并上调p53及半胱天冬酶3(caspase-3)的表达。与非纳米HMC相比,NHMC能够更快地被细胞摄取并引起更多的肿瘤细胞凋亡。NHMC对正常皮肤细胞无明显细胞毒性。结论:使用生物可降解材料PLGA制成的小分子纳米颗粒NHMC能够更快速地被细胞摄取并引起更多的肿瘤细胞凋亡,而对正常皮肤细胞无明显细胞毒性。提取天然药用植物中的有效成分制成纳米颗粒胶囊有望成为更好地发挥其药效的途径。
OBJECTIVE: Scopolatin (7-hydroxy-6-methoxycoumarin, chemical formula C10H8O4, referred to as HMC) is a natural coumarin extracted from Gelsemium sempervirens and is believed to have Anti-cancer activity. In this study, HMC was made into polylactic-co-glycolic acid (PLGA) nanoparticle capsules, and compared with non-nano-HMC by a number of indicators to determine the cell uptake, bioavailability and The impact of apoptosis (anti-cancer activity) and other areas have improved. Methods: Human melanoma A375 cells were used to detect the cellular uptake rate and anticancer activity of HMC and nano-7-hydroxy-6-methoxy coumarin (NHMC). The particle size of NHMC was determined by dynamic light scattering Dispersibility index and electrokinetic potential; scanning electron microscopy and atomic force microscopy to detect the surface morphology of the nanoparticles. Results: The entrapment efficiency of HMC nanoparticle capsules was over 85%. The mean diameter of NHMC particles was less than 110 nm with a polydispersity coefficient of 0.237, which increased their cellular uptake and bioactivity. NHMCs were significantly uptake by cells (15 min) significantly less than non-nano HMCs (30 min). The mRNA expression of certain signaling molecules in the cells was measured, indicating that NHMC can downregulate the expressions of cyclin-D1, PCNA, survivin and signal transducers and activators of transcription 3 ( Stat-3) and upregulate the expression of p53 and caspase-3. NHMCs are more rapidly taken up by cells and cause more tumor cells to apoptosis than non-nano-HMCs. NHMC on normal skin cells without significant cytotoxicity. Conclusion: NHPM, a small molecule nanoparticle made of biodegradable material PLGA, can be taken up by cells more rapidly and cause more apoptosis of tumor cells, but no obvious cytotoxicity on normal skin cells. Extraction of the active ingredients of natural medicinal plants made of nano-capsules is expected to be a better way to play its efficacy.