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Title of Journal: Pharm Res

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Abbravation: Pharmaceutical Research

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Springer US

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DOI

10.1002/ardp.18651710169

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1573-904X

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Polyplex Micelles from Triblock Copolymers Compose

Authors: Kanjiro Miyata Makoto Oba Mitsunobu R Kano Shigeto Fukushima Yelena Vachutinsky Muri Han Hiroyuki Koyama Kohei Miyazono Nobuhiro Nishiyama Kazunori Kataoka
Publish Date: 2008/09/10
Volume: 25, Issue: 12, Pages: 2924-2936
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Abstract

For systemic gene delivery to pancreatic tumor tissues we prepared a threelayered polyplex micelle equipped with biocompatibility efficient endosomal escape and pDNA condensation functions from three components tandemly aligned polyethylene glycol PEG a polyaspartamide derivative with a 12diaminoethane moiety PAspDET and polyllysineThe size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering DLS and luciferase assay respectively The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein EGFP expression in the tumor tissuesThe polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control With the aid of transforming growth factor TGFβ type I receptor TβR1 inhibitor which enhances accumulation of macromolecular drugs in tumor tissues the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor BxPC3 tissues mainly in the stromal regions including the vascular endothelial cells and fibroblastsThis work was financially supported by the Core Research Program for Evolutional Science and Technology CREST from the Japan Science and Technology Corporation JST as well as by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education Culture Sports Science and Technology of Japan MEXT

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