Journal
BIOMATERIALS
Volume 33, Issue 18, Pages 4722-4730Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.03.017
Keywords
DNA; Micelle; Nanoparticle; Gene transfer; In vitro test; In vivo test
Funding
- Japan Science and Technology Corporation (JST)
- Japan Society for the Promotion of Science (JSPS)
- Center for Medical System Innovation (CMSI) (Global COE, MEXT)
- Ministry of Education, Science, Sports and Culture, Japan (MEXT)
- Grants-in-Aid for Scientific Research [23350049, 23790433, 22750098, 10F00337] Funding Source: KAKEN
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Homo-poly(N'-[N-(2-aminoethyl)-2-aminoehtyljaspartamide) [PAsp(DET), HI was attempted to integrate into poly (ethylene glycol) (PEG)-b-PAsp(DET)] (B) formulated polyplex micelle with the aim of enhancing cell transfection efficiency for PEGylated polyplex micelle via H integration. In vitro evaluations verified H integration of potent stimulation in enhancing cell-transfecting activity of PEGylated polyplex micelles via promoted cellular uptake and facilitated endosome escape. In vivo anti-angiogenic tumor suppression evaluations validated the feasibility of H integration in promoting gene transfection to the affected cells via systemic administration, where loaded anti-angiogenic gene remarkably expressed in the tumor site, thereby imparting significant inhibitory effect on the growth of vascular endothelial cells, ultimately leading to potent tumor growth suppression. These results demonstrated potency of H integration for enhanced transfection activity and potential usage in systemic applications, which could have important implications on the strategic use of H integration in the non-viral gene carrier design. (C) 2012 Elsevier Ltd. All rights reserved.
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