RRC ID 43460
Author Miyata K, Oba M, Kano MR, Fukushima S, Vachutinsky Y, Han M, Koyama H, Miyazono K, Nishiyama N, Kataoka K.
Title Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue.
Journal Pharm. Res.
Abstract PURPOSE:For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(L-lysine).
MATERIALS AND METHODS:The 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 tissues.
RESULTS:The 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 (TGF)-beta type I receptor (TbetaR-1) 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 fibroblasts.
CONCLUSION:The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.
Volume 25(12)
Pages 2924-36
Published 2008-12
DOI 10.1007/s11095-008-9720-2
PMID 18781378
MeSH Animals Biocompatible Materials / chemistry Cell Line, Tumor DNA / administration & dosage* Endosomes / metabolism* Female Gene Transfer Techniques* Genetic Therapy* Humans Mice Mice, Inbred BALB C Micelles Pancreatic Neoplasms / therapy* Peptides / administration & dosage* Peptides / chemistry Peptides / pharmacokinetics Polyethylene Glycols / chemistry Polylysine / chemistry Polymers / administration & dosage* Polymers / chemistry Polymers / pharmacokinetics Protein-Serine-Threonine Kinases / antagonists & inhibitors Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta / antagonists & inhibitors Transfection
IF 3.335
Times Cited 31
WOS Category PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY
Resource
Human and Animal Cells