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Transferrin-PEG-PE modified dexamethasone conjugated cationic lipid carrier mediated gene delivery system for tumor-targeted transfection

Authors Wang W, Zhou F, Ge L, Liu X, Kong F

Received 18 March 2012

Accepted for publication 10 April 2012

Published 21 May 2012 Volume 2012:7 Pages 2513—2522

DOI https://doi.org/10.2147/IJN.S31915

Review by Single-blind

Peer reviewer comments 2

Wei Wang,1 Fang Zhou,2 Linfu Ge,2 Ximin Liu,2 Fansheng Kong2

1Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji’nan Command, Ji’nan, China; 2Department of Hematology, General Hospital of Ji’nan Command, Ji’nan, China

Background: The main barriers to non-viral gene delivery include cellular and nuclear membranes. As such, the aim of this study was to develop a type of vector that can target cells through receptor-mediated pathways and by using nuclear localization signal (NLS) to increase the nuclear uptake of genetic materials.
Methods: A dexamethasone (Dexa)-conjugated lipid was synthesized as the material of the solid lipid nanoparticles (SLNs), and transferrin (Tf) was linked onto polyethylene glycol-phosphatidylethanolamine (PEG-PE) to obtain Tf-PEG-PE ligands for the surface modification of the carriers. The in vitro transfection efficiency of the novel modified vectors was evaluated in human hepatoma carcinoma cell lines, and in vivo effects were observed in an animal model.
Results: Tf-PEG-PE modified SLNs/enhanced green fluorescence protein plasmid (pEGFP) had a particle size of 222 nm and a gene loading quantity of 90%. Tf-PEG-PE-modified SLNs/pEGFP (Tf-SLNs/pEGFP) displayed remarkably higher transfection efficiency than non-modified SLNs/pEGFP and the vectors not containing Dexa, both in vitro and in vivo.
Conclusion: It can be concluded that Tf and Dexa could function as an excellent active targeting ligand to improve the cell targeting and nuclear targeting ability of the carriers, and the resulting nanomedicine could be a promising active targeting drug/gene delivery system.

Keywords: gene delivery, active targeting, transferrin-PEG-PE, dexamethasone conjugated lipid, nuclear localization

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