Details

Autor(en) / Beteiligte

• Aliabadi, Hamidreza Montazeri
• Landry, Breanne
• Bahadur, Remant K.
• Neamnark, Artphop
• Suwantong, Orawan
• Uludağ, Hasan

Titel

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

Ist Teil von

• Macromolecular bioscience, 2011-05, Vol.11 (5), p.662-672

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2011

Quelle

Wiley Online Library Journals【Remote access available】

Beschreibungen/Notizen

• Characterization of a polymer library engineered to enhance their ability to protect and deliver their nucleotide cargo to the cells is reported. The ζ‐potential continuously increased with higher polymer:siRNA weight ratio, and the ζ‐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. It is demonstrated that lipid substitution on non‐toxic, low‐MW PEI yields an effective siRNA carrier without increasing its toxicity significantly. Lipid substitution enhances the ζ‐potential of complexes formed between the polymers and siRNA, indicating a better assembly of the complexes as a result of lipid substitution. Lipid substitution further improved the protective effect of polymers in serum and significantly enhanced siRNA delivery into cells. Effective silencing of target proteins was achieved with the designed carriers in drug‐resistant cancer cells.