聚乙二醇接枝率对第五代聚酰胺-胺树状大分子体外毒性与细胞摄取的影响

发布时间：2018-07-10 13:52

本文选题：第五代聚酰胺-胺树状大分子 + 聚乙二醇　；参考：《中国药学杂志》2017年01期

【摘要】：目的研究聚乙二醇(PEG)不同接枝率对第五代聚酰胺-胺(polyanfido-amine,PAMAM G5)树状大分子体外毒性与细胞摄取的影响。方法合成4种不同接枝率的PEG-PAMAM G5,采用核磁共振氢谱(~1H-NMR)、红外光谱(FT-IR)、纳米粒度-电位分析仪进行结构鉴定和表征,溶血毒性和细胞毒性实验考察体外安全性,细胞摄取实验及激光共聚焦显微镜考察摄取情况及胞内定位。结果 4种PEG-PAMAM G5的PEG接枝率分别为7.8%,14.1%,20.3%和24.2%,粒径依次为(17.05±1.77)nm(20.77±1.02)nm(21.68±1.04)nm(23.19±0.54)nm,Zeta电位由PAMAM G5的(25.57±1.37)mV降低至PEG_(31)-PAMAM G5的(9.27±0.40)mV。PAMAM G5经PEG修饰后,溶血毒性、细胞毒性和细胞摄取均显著降低(P0.05),仍可被HBMEC细胞摄取并进入细胞核。结论 PEG修饰可显著降低PAMAM G5的体外细胞毒性,随着PEG接枝率的增大,Zeta电位降低,减毒效果越显著;经修饰后的PEG-PAMAM G5仍具有进入细胞核的能力。因此,PEG化树状大分子可作为基因或细胞核靶向药物的载体进行更深入的研究。
[Abstract]:Objective to study the effects of different grafting rates of polyethylene glycol (PEG) on the in vitro toxicity and cell uptake of the fifth generation polyanfido-amineamine (PAMAM G5) dendritic macromolecules. Methods four kinds of PEG-PAMAM G5 with different grafting rates were synthesized. The structures of PEG-PAMAM G5 were identified and characterized by 1H-NMR, FT-IR and nano-particle size potential analyzer. The in vitro safety of PEG-PAMAM G5 was investigated by hemolytic and cytotoxicity tests. Cell uptake test and laser confocal microscopy were used to investigate the uptake and intracellular localization. Results the PEG grafting rates of the four PEG-PAMAM G5 were 7.8% and 24.2%, respectively. The diameter of PEG-PAMAM G5 was (17.05 卤1.77) nm (20.77) nm (20.77 卤1.02) nm (21.68 卤1.04) nm (23.19 卤0.54) nm (Zeta potential decreased from (25.57 卤1.37) MV of PamAM-G5 to (9.27 卤0.40) MV of PEG31 -PAMAM G5 modified with PEG5, and the hemolytic toxicity of PEG-PAMAM G5 was decreased from (25.57 卤1.37) MV to (9.27 卤0.40) MV. Cytotoxicity and cellular uptake were significantly decreased (P0.05), and HBMEC cells could still uptake and enter the nucleus. Conclusion PEG modification can significantly reduce the cytotoxicity of PamAM-G5 in vitro, and with the increase of PEG grafting rate, the cytotoxicity of PEG-PAMAM-G5 can still enter the nucleus of PEG-PAMAM G5. Therefore, PEG-based dendrimers can be used as carriers for gene or nuclear targeting drugs.
【作者单位】：浙江中医药大学药学院;
【基金】：国家自然科学基金资助项目(81274089) 浙江省自然科学基金资助项目(LY12H28004)
【分类号】：R943

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