Journal
BIOMATERIALS
Volume 30, Issue 29, Pages 5844-5852Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.07.017
Keywords
Gene therapy; Non-viral vector; Aerosol delivery; Folate-chitosan-graft-polyethylenimine; Akt1 shRNA; Lung tumorigenesis
Funding
- Korea Research Foundation (KRF) [E00244]
- National Instrumentation Center for Environmental Management (NICEM)
- Brain Korea 21 Program for Veterinary Science
- National Research Foundation of Korea [2008-314-E00244, 과C6A2206] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 H-1 nuclear magnetic resonance (H-1 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. (C) 2009 Elsevier Ltd. All rights reserved.
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