• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

PEG可脱除材料修饰miRNA纳米粒的制备以及体内外性质的考察

曾叶, 周子楦, 孙逊

曾叶, 周子楦, 孙逊. PEG可脱除材料修饰miRNA纳米粒的制备以及体内外性质的考察[J]. 中国药科大学学报, 2016, 47(6): 702-707. DOI: 10.11665/j.issn.1000-5048.20160612
引用本文: 曾叶, 周子楦, 孙逊. PEG可脱除材料修饰miRNA纳米粒的制备以及体内外性质的考察[J]. 中国药科大学学报, 2016, 47(6): 702-707. DOI: 10.11665/j.issn.1000-5048.20160612
ZENG Ye, ZHOU Zixuan, SUN Xun. Preparation of sheddable PEG modified miRNA-complexing nanoparticles and its preliminary in vitro and in vivo study[J]. Journal of China Pharmaceutical University, 2016, 47(6): 702-707. DOI: 10.11665/j.issn.1000-5048.20160612
Citation: ZENG Ye, ZHOU Zixuan, SUN Xun. Preparation of sheddable PEG modified miRNA-complexing nanoparticles and its preliminary in vitro and in vivo study[J]. Journal of China Pharmaceutical University, 2016, 47(6): 702-707. DOI: 10.11665/j.issn.1000-5048.20160612

PEG可脱除材料修饰miRNA纳米粒的制备以及体内外性质的考察

基金项目: 国家自然科学基金资助项目(No.81422044)

Preparation of sheddable PEG modified miRNA-complexing nanoparticles and its preliminary in vitro and in vivo study

  • 摘要: 制备PEG可脱除材料修饰miRNA纳米粒,考察其细胞摄取以及体内分布情况。采用酰胺键缩合的方法合成可被β-环糊精包合的金刚烷修饰的PEG材料,通过静电作用与miR-34a复合制得纳米粒,加入与β-环糊精亲和力更高的布洛芬后可置换脱除纳米粒的PEG壳,测定该PEG可脱除纳米粒的粒径和Zeta电位;考察其在4T1细胞上的摄取能力以及在荷有4T1细胞的BALB/c小鼠体内的分布情况。结果显示,可被β-环糊精包合的金刚烷修饰的PEG材料合成成功;通过静电作用与miR-34a复合后制得的PEG可脱除纳米粒,粒径为107.7 nm,Zeta电位为15.8 mV;相比于PEG未脱除的纳米粒,被4T1细胞摄取的能力与在小鼠体内肿瘤部位的浓度都有显著提高,该体系在肿瘤治疗领域的应用具有很大的潜力。
    Abstract: This study was aimed to prepare sheddable PEG modified miRNA-complexing nanoparticles and investigate in vitro cellular uptake effect and in vivo distribution profile. The sheddable PEG material was synthesized through condensation. The sheddable PEG modified miRNA-complexing nanoparticles were successfully prepared by electrostatic interaction between gene vector and miRNA, and then ibuprofen was added to deshield PEG layer. The in vitro cellular uptake effect and in vivo distribution profile of nanoparticles were investigated on 4T1 model cells. As a result, the particle size of nanoparticles was 107. 7 nm and Zeta potential was 15. 8 mV. Compared to unsheddable PEG group, the cellular uptake effect by 4T1 tumor cells as well as the concentration on tumor regions was significantly improved in the sheddable PEG group. Results showed that this systen has a great potential application in the field of tumor treatment.
  • [1] Bartel DP.MicroRNAs:target recognition and regulatory functions[J].Cell,2009,136(2):215-233.
    [2] Ventura A, Jacks T. MicroRNAs and cancer: short RNAs go a long way[J].Cell,2009,136(4):586-591.
    [3] Zhu L,Mahato RI.Targeted delivery of siRNA to hepatocytes and hepatic stellate cells by bioconjugation[J].Bioconjug Chem,2010,21(11):2119-2127.
    [4] Li FY,Zhou JP,Wu XM,et al.Formula optimization and transfection efficiency of polyethyleneimine/DNA complexes[J].J China Pharm Univ(中国药科大学学报),2010,41(1):40-44.
    [5] Dash PR, Read ML, Barrett LB, et al. Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery [J].Gene Ther,1999,6(4):643-650.
    [6] Caplen NJ.Gene therapy progress and prospects.Downregulating gene expression:the impact of RNA interference [J].Gene Ther,2004,11(16):1241-1248.
    [7] Vile RG,Russell SJ,Lemoine NR.Cancer gene therapy:hard lessons and new courses [J].Gene Ther,2000,7(7):2-8.
    [8] Li YH,Zong L,Zhu JB,et al.Formulation optimization of PEGylated cationic liposomes as siRNA delivery system [J].J China Pharm Univ(中国药科大学学报),2011,42(5):412-417.
    [9] Mishra S, Webster P, Davis ME, et al. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles [J].Eur J Cell Biol,2004,83(3):97-111.
    [10] Pun SH,Bellocq NC,Liu A,et al.Cyclodextrin-modified polyethylenimine polymers for gene delivery [J].Bioconjug Chem,2004,15(4):831-840.
    [11] Larsen KL,Endo T,Ueda H,et al.Inclusion complex formation constants of α-,β-,γ-,δ-,ε-,ζ-,η- and θ-cyclodextrins determined with capillary zone electrophoresis [J].Carbohydr Res,1998,309(309):153-159.
计量
  • 文章访问数:  692
  • HTML全文浏览量:  0
  • PDF下载量:  1087
  • 被引次数: 0
出版历程
  • 刊出日期:  2016-12-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭