Impact of Lipid Substitution on Assembly and Delivery of siRNA by Cationic Polymers

被引:79
作者
Aliabadi, Hamidreza Montazeri [1 ]
Landry, Breanne [1 ]
Bahadur, Remant K. [1 ]
Neamnark, Artphop [4 ,5 ]
Suwantong, Orawan [4 ,5 ]
Uludag, Hasan [1 ,2 ,3 ]
机构
[1] Univ Alberta, Dept Chem & Mat Engn, Fac Engn, Edmonton, AB T6G 2V4, Canada
[2] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2V4, Canada
[3] Univ Alberta, Dept Biomed Engn, Fac Med, Edmonton, AB T6G 2V4, Canada
[4] Chulalongkorn Univ, Petr & Petrochem Coll, Bangkok, Thailand
[5] Chulalongkorn Univ, Ctr Petr Petrochem & Adv Mat, Bangkok, Thailand
基金
加拿大自然科学与工程研究理事会;
关键词
cancer; down-regulation; polymers; self-assembly; siRNA; GENE DELIVERY; IN-VIVO; LINEAR POLYETHYLENIMINE; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; RNAI; CELLS; DNA; POLY(ETHYLENIMINE); CARRIERS;
D O I
10.1002/mabi.201000402
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Characterization of a polymer library engineered to enhance their ability to protect and deliver their nucleotide cargo to the cells is reported. The zeta-potential continuously increased with higher polymer: siRNA weight ratio, and the zeta-potential of lipid-modified polymers: siRNA complexes were higher than PEI2 at all ratios. At polymer: siRNA ratio of 1: 1, all lipid-substituted polymers showed complete protection against degradation. Lipid-modified polymers significantly increased the cellular uptake of siRNA complexes and down-regulation of GAPDH and P-gp (max. 66% and 67%, respectively). The results indicate that hydrophobic modification of low molecular PEI could render this otherwise ineffective polymer to a safe effective delivery system for intracellular siRNA delivery and protein silencing.
引用
收藏
页码:662 / 672
页数:11
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