Effective tumor treatment by VEGF siRNA complexed with hydrophobic poly(amino acid)-modified polyethylenimine.

Abstract

Two copolymers are designed and synthesised for siRNA delivery based on polyethylenimine by grafting hydrophilic acrylamide segments and hydrophobic poly(γ-benzyl L-glutamate). The amphiphilic PEI-PBLG/siRNA complex demonstrates high gene silencing efficiency in the absence or presence of 10 vol% and 50 vol% sera in vitro. The anti-tumor effects in vivo are evaluated in luciferase-bearing mice expressing CT26 tumors. PEI-PBLG/siVEGF complex provides a higher and more sustained suppressive effect by reducing VEGF mRNA expression in the tumors, leading to higher tumor growth inhibition efficacy. Further studies on the potential use of the PEI-PBLG carrier system in mediating the silencing of genes other than VEGF or in other tumor models are recommended.

• Authors: Jie Chen, Huayu Tian, Xuan Dong, Zhaopei Guo, Zixue Jiao, Feifan Li, Arihiro Kano, Atsushi Maruyama, Xuesi Chen
• Journal: Macromolecular bioscience (Macromol Biosci) Vol. 13 Issue 10 Pg. 1438-46 (Oct 2013) ISSN: 1616-5195 [Electronic] Germany
• PMID: 23873676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Polymers
• RNA, Messenger
• RNA, Small Interfering
• Vascular Endothelial Growth Factor A
• polyethylenimine-poly(gamma-benzylglutamate)
• Polyglutamic Acid
• Polyethyleneimine

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Silencing
• Genetic Therapy
• Humans
• Hydrophobic and Hydrophilic Interactions
• Mice
• Polyethyleneimine (administration & dosage, analogs & derivatives, chemistry)
• Polyglutamic Acid (administration & dosage, analogs & derivatives, chemistry)
• Polymers (administration & dosage, chemistry)
• RNA, Messenger (biosynthesis)
• RNA, Small Interfering (administration & dosage, chemistry, genetics)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, biosynthesis, genetics)