叶酸修饰的纳米结构脂质载体用于基因靶向癌症治疗的研究

发布时间：2018-06-11 18:03

本文选题：卵巢癌 + 纳米结构脂质载体　；参考：《中国新药杂志》2017年06期

【摘要】：目的:本文旨在制备叶酸(folate,FA)修饰的纳米结构脂质载体(FA-NLC)作为基因药物(p DNA)传递载体,并研究FA-NLC/p DNA的药剂学和生物学特性。方法:通过FA与DSPE-PEG2000-NH2发生酰胺反应生成FA-PEG2000-DSPE;采用熔融乳化法制备阳离子NLC,与p DNA复合,制备NLC/p DNA;以合成的FA-PEG2000-DSPE对NLC/p DNA进行表面修饰,制得FA-NLC/p DNA。本研究对NLC的体外相关性质进行了初步评价,并对粒径、Zeta电位、包封率、体外细胞毒性及细胞转染效率等方面与市售Lipofectamin湟3000进行了对比。结果:FA-NLC/p DNA平均粒径为(143.8±5.1)nm,多聚分散度(PDI)为(0.19±0.04),Zeta电位为(12.1±2.9)m V,p DNA结合率为(90.6±2.7)%;FA-NLC/p DNA组60 h基因的累积释放率为80%,较NLC/p DNA组及Lipofectamin湟3000组释放更为缓慢;48 h的细胞转染率显著强于NLC/p DNA组和Lipofectamin湟3000组,且无明显细胞毒性。结论:上述结果表明,FA-NLC有潜力成为高效低毒的非病毒型基因药物传递载体。
[Abstract]:Aim: to prepare folate- FA-modified lipid carrier (FA-NLC) as a transporter for gene drug pDNA, and to study the pharmacological and biological characteristics of FA-NLC / p DNA. Methods: FA-PEG2000-DSPE was formed by amide reaction of FA with DSPE-PEG2000-NH2, cationic NLCs / p DNA was prepared by melt emulsification method, and NLC / p DNA was prepared by surface modification of NLC / p DNA with synthesized FA-PEG2000-DSPE, and FA-NLCp-DNAs were prepared by surface modification of the synthesized FA-PEG2000-DSPE. In this study, the properties of NLC in vitro were preliminarily evaluated, and the particle size Zeta potential, entrapment efficiency, cytotoxicity and transfection efficiency of NLC were compared with those of Lipofectamin Huang 3000. Results the average particle size of DNA was 143.8 卤5.1 nm, the polydispersity PDI was 0.19 卤0.04, the Zeta potential was 12.1 卤2.9 mVP DNA binding rate was 90.6 卤2.7%, the cumulative release rate of 60h gene in FA-NLCp DNA group was 80. The cell transfection rate was significantly higher than that in NLCP DNA group and Lipofectamin 3000 group for 48 h. The cell transfection rate was significantly lower than that in NLCP DNA group and Lipofectamin 3000 group, and the cell transfection rate was significantly higher than that in NLCP DNA group and Lipofectamin 3000 group. The cell transfection rate was significantly higher than that in NLCP DNA group and Lipofectamin 3000 group. NLC / p DNA group and Lipofectamin 3000 group, There was no obvious cytotoxicity. Conclusion: these results suggest that FA-NLC has the potential to be a highly efficient and low virulent non-viral gene drug delivery vector.
【作者单位】：上海鲁源医药科技有限公司;
【分类号】：R943

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