共 27 条
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.
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页码:662 / 672
页数:11
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