乙酰化可降低聚酰胺-胺的细胞毒性****☆◆

摘要

背景：聚酰胺-胺型树枝状高分子纳米材料已被广泛应用于药物载体的研究，但由于整代聚酰胺-胺表面有大量带正电荷的氨基，具有一定的细胞毒性。目的：观察乙酰化对聚酰胺-胺细胞毒性的影响。方法：①细胞增殖检测：采用 MTT 法检测在含0，0.125，0.25，0.5，1，2，4μmol/L 乙酰化聚酰胺-胺的培养液中人胚肾293T 细胞的增殖。②细胞形态：倒置荧光显微镜观察在含4μmol/L 乙酰化聚酰胺-胺的培养液中人胚肾293T 细胞的形态。③细胞周期：流式细胞术检测在含0，5，10，15，20 mg/L 乙酰化聚酰胺-胺的培养液中人胚肾293T 细胞的细胞周期。结果与结论：聚酰胺-胺对293T 细胞具有一定的细胞毒性，在4μmol/L 浓度下48 h 的细胞存活率仅为52%，而乙酰化可显著降低聚酰胺-胺的细胞毒性(P <0.01)；聚酰胺-胺孵育的细胞发生团缩，伸展性变差，而乙酰化聚酰胺-胺孵育的293T 细胞与正常培养细胞基本一致，具有良好的伸展性；乙酰化聚酰胺-胺对细胞周期无影响，而聚酰胺-胺在20 mg/L 较高质量浓度时可使细胞 S 期产生阻滞。表明乙酰化可以降低聚酰胺-胺的细胞毒性。%BACKGROUND: Polyamidoamine dendrimer nanomaterials have been widely used in drug carrier research, but there are many electropositive amino groups on the surface of the entire generation polyamidoamine, resulting in certain cytotoxicity.OBJECTIVE: To study the influence of acetylation on polyamidoamine cytotoxicity. METHODS: (1) 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay: the cel proliferation of 293T cells incubated with acetylated polyamidoamine under 0, 0.125, 0.25, 0.5, 1, 2, 4 μmol/L concentrations was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. (2) Cel morphology: the cel morphology of 293T cells incubated with 4 μmol/L acetylated polyamidoamine was observed by inverted fluorescence microscope. (3) Cel cycle: the cel cycle of 293T cells incubated with acetylatedpolyamidoamine under 0, 5, 10, 15, 20 mg/L concentrations was detected by flow cytometry. RESULTS AND CONCLUSION: Polyamidoamine had cytotoxicity to 293T cells. The cel viability at 4 μmol/L concentration after 48 hours incubation was only 52%, and the acetylation could significantly decrease the cytotoxicity of polyamidoamine (P < 0.01). 293T cells incubated with polyamidoamine shrank and had bad stretching, while 293T cells incubated with acetylated polyamidoamine had good stretching. Acetylated polyamidoamine had no significant effect on the cel cycle, but polyamidoamine at 20 mg/L could block the cel cycle at S stage. Al the results show that acetylation can decrease the cytotoxicity of polyamidoamine.