Journal
BIOMATERIALS
Volume 31, Issue 24, Pages 6344-6354Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.04.047
Keywords
NGR peptide; Polyethylenimine; Reducible; Tumor targeting; Gene delivery
Funding
- Ministry of Education, Science and Technology [20090068098, 20100002175]
- Ministry of Knowledge Economy, Republic of Korea [K0006028]
Ask authors/readers for more resources
The work demonstrated development of multifunctional gene carrier which has incorporated reducible moiety, tumor targeting ligands as well as PEG to achieve efficient release of pDNA, enhanced tumor-specificity and long circulation, respectively. In our successful one-pot synthesis of multifunctional polymer, low molecular weight branched polyethylenimine (BPEI) was thiolated with propylene sulfide, and mixed with alpha-Maleimide-omega-N-hydroxysuccinimide ester polyethylene glycol (MAL-PEG-NHS. MW: 5000), and cyclic NGR peptide. The structural elucidation of the cNGR conjugated reducible BPEI containing disulfide bond (BPEI-SS-PEG-cNGR), was done by NMR and GPC study. Complex formation as well as reducible property of the polymer was confirmed by gel retardation assay. In order to achieve efficient tumor targeting, we have used cNGR peptide which is known to bind to CD13 overexpressed in neovasculature endothelial cells. Tumor target-specificity of polymer was established by carrying out competitive inhibition assay with free cNGR peptide. Cellular uptake of polymers was evaluated by confocal laser scanning microscope (CLSM). Finally, addition of free cNGR and buthionine sulfoximine (BSO) reduced transfection efficiency synergistically, which implied that multifunctional polymer-mediated gene transfection took place tumor-specifically and via GSH-dependent pathway. (C) 2010 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available