Journal
BIOMATERIALS
Volume 32, Issue 2, Pages 652-663Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.09.022
Keywords
Non viral gene vector; Polyplex micelle; Cholesterol; Pancreatic tumor; Anti anglogenic therapy
Funding
- Japan Science and Technology Agency (JST)
- [20689024]
- Grants-in-Aid for Scientific Research [22750098] Funding Source: KAKEN
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Polyplex micelles formed with plasmic! DNA (pDNA) and poly(ethylene glycol) (PEG)-block-poly(N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide) [PAsp(DET)] exhibit effective endosomal escaping properties based on di-protonation of diamine side chains with decreasing pH which improves their transfection efficiency and thus are promising candidates for local in vivo gene transfer Here PEG-PAsp(DET) polyplex micelles were further Improved as in vivo systemic vectors by introduction of cholesterol (Chole) into the vi-terminus of PEG-PAsp(DET) to obtain PEG-PAsp(DET)-Chole Introduction of the cholesterol resulted in enhanced association of block copolymers with pDNA which led to increased stability in proteinous medium and also in the blood stream after systemic injection compared to PEG-PAsp(DET) micelles The synergistic effect between enhanced polymer association with pDNA and increased micelle stability of PEG-PAsp(DET)-Chole polyplex micelles led to high in vitro gene transfer even at relatively low concentrations due to efficient cellular uptake and effective endosomal escape of block copolymers and pDNA Finally PEG-PAsp(DET)-Chole micelles achieved significant suppression of tumor growth following Intravenous injection Into mice bearing a subcutaneous pancreatic tumor using therapeutic pDNA encoding an anti-angiogenic protein These results suggest that PEG-PAsp(DET)-Chole micelles can be effective systemic gene vectors for treatment of solid tumors (C) 2010 Elsevier Ltd All rights reserved
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