fulltext.study @t Gmail

The suppression of lung tumorigenesis by aerosol-delivered folate–chitosan-graft-polyethylenimine/Akt1 shRNA complexes through the Akt signaling pathway

Paper ID Volume ID Publish Year Pages File Format Full-Text
8955 610 2009 9 PDF Available
Title
The suppression of lung tumorigenesis by aerosol-delivered folate–chitosan-graft-polyethylenimine/Akt1 shRNA complexes through the Akt signaling pathway
Abstract

RNA interference (RNAi) represents a promising new approach to the inhibition of gene expression in vitro and in vivo, and has therapeutic potential for human diseases. Efficient delivery of small interfering RNA (siRNA) or small hairpin RNA (shRNA) is a critical concern in RNAi studies. Here we report the development of a new polymeric gene carrier for cancer cell-targeting, designed to enhance the intracellular delivery of shRNA and reduce cytotoxicity. Folate–chitosan-graft-polyethylenimine (FC-g-PEI) copolymer was prepared by an imine reaction between periodate-oxidized folate–chitosan (FC) and low molecular weight polyethylenimine (PEI). FC-g-PEI copolymer was investigated as a potential cancer cell-targeting gene carrier. The composition of FC-g-PEI was characterized using 1H nuclear magnetic resonance (1H NMR), and particle size and zeta potential of FC-g-PEI/shRNA complexes were measured using dynamic light scattering (DLS). FC-g-PEI showed good shRNA condensation ability and high protection of shRNA from nuclease attack. It also exhibited lower cytotoxicity compared to PEI 25K control, and showed good cancer cell-targeting ability. Furthermore, aerosol delivery of FC-g-PEI/Akt1 shRNA complexes suppressed lung tumorigenesis in a urethane-induced lung cancer model mouse through the Akt signaling pathway. Together, these results suggest that FC-g-PEI may be useful for shRNA-based gene therapy.

Keywords
Gene therapy; Non-viral vector; Aerosol delivery; Folate–chitosan-graft-polyethylenimine; Akt1 shRNA; Lung tumorigenesis
First Page Preview
The suppression of lung tumorigenesis by aerosol-delivered folate–chitosan-graft-polyethylenimine/Akt1 shRNA complexes through the Akt signaling pathway
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 29, October 2009, Pages 5844–5852
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering