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通过阳离子脂质体将质粒DNA和反义寡脱氧核糖核苷酸共同递送至人癌细胞。

Co-delivery of plasmid DNA and antisense oligodeoxyribonucleotide into human carcinoma cells by cationic liposomes.

作者信息

Weecharangsan Wanlop, Opanasopit Praneet, Yingyongnarongkul Boon-ek, Kewsuwan Prartana, Lee Robert J

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy Srinakharinwirot University, Nakhonnayok 26120, Thailand.

出版信息

Curr Pharm Biotechnol. 2014;15(9):790-9. doi: 10.2174/1389201015666141020154352.

Abstract

This study aimed to evaluate the co-delivery of cationic liposome/plasmid DNA complexes and cationic liposome/antisense oligodeoxyribonucleotide (AS ODN) complexes in HeLa human cervical carcinoma cells. Dimethyldioctadecyl ammonium bromide (DDAB): dioleoyl phosphatidylethanolamine (DOPE) liposome/plasmid DNA complexes, and DDAB:DOPE liposome/AS ODN complexes were formulated and characterized in terms of agarose gel electrophoretic mobility, particle size and zeta potential. The complexes were evaluated for delivery of pEGFP plasmid DNA and AS ODN in HeLa cells. Cell growth inhibition was evaluated using p53 plasmid DNA and bcl-2 AS ODN, by codelivery of DDAB:DOPE liposome/p53 plasmid DNA and DDAB:DOPE liposome/bcl-2 AS ODN complexes. The particle size of DDAB:DOPE liposome/plasmid DNA complexes, and DDAB:DOPE liposome/AS ODN complexes were 180.6±2.0 to 372.3±2.4 nm, and zeta potentials were -26.7±1.2 to +6.8±0.4 mV, respectively. The AS ODN uptake and green fluorescent protein (GFP) expression upon their co-delivery by DDAB:DOPE liposomes were both high. Treatment of the cells with the co-delivery of DDAB:DOPE liposome/p53 plasmid DNA complexes and DDAB:DOPE liposome/ bcl-2 AS ODN complexes inhibited cell growth to a greater degree than that with either DDAB:DOPE liposome/p53 plasmid DNA complexes or DDAB:DOPE liposome/bcl-2 AS ODN complexes alone. These data suggest that co-delivery of cationic liposome/p53 plasmid DNA and cationic liposome/bcl-2 AS ODN complexes is an effective strategy to achieve enhanced therapeutic activities.

摘要

本研究旨在评估阳离子脂质体/质粒DNA复合物与阳离子脂质体/反义寡脱氧核苷酸(AS ODN)复合物在人宫颈癌HeLa细胞中的共递送情况。制备了二甲基二十八烷基溴化铵(DDAB):二油酰磷脂酰乙醇胺(DOPE)脂质体/质粒DNA复合物以及DDAB:DOPE脂质体/AS ODN复合物,并从琼脂糖凝胶电泳迁移率、粒径和ζ电位方面对其进行了表征。评估了这些复合物在HeLa细胞中递送pEGFP质粒DNA和AS ODN的情况。通过共递送DDAB:DOPE脂质体/p53质粒DNA和DDAB:DOPE脂质体/bcl-2 AS ODN复合物,利用p53质粒DNA和bcl-2 AS ODN评估细胞生长抑制情况。DDAB:DOPE脂质体/质粒DNA复合物以及DDAB:DOPE脂质体/AS ODN复合物的粒径分别为180.6±2.0至372.3±2.4 nm,ζ电位分别为-26.7±1.2至+6.8±0.4 mV。DDAB:DOPE脂质体共递送AS ODN和绿色荧光蛋白(GFP)时,二者的摄取量均很高。与单独使用DDAB:DOPE脂质体/p53质粒DNA复合物或DDAB:DOPE脂质体/bcl-2 AS ODN复合物相比,共递送DDAB:DOPE脂质体/p53质粒DNA复合物和DDAB:DOPE脂质体/bcl-2 AS ODN复合物对细胞生长的抑制作用更强。这些数据表明,阳离子脂质体/p53质粒DNA与阳离子脂质体/bcl-2 AS ODN复合物的共递送是实现增强治疗活性的有效策略。

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