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.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
authors.forename: Kanjiro
authors.initials: K
authors.lastname: Miyata
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.forename: Mitsunobu R
authors.initials: MR
authors.lastname: Kano
authors.forename: Shigeto
authors.initials: S
authors.lastname: Fukushima
authors.forename: Yelena
authors.initials: Y
authors.lastname: Vachutinsky
authors.forename: Muri
authors.initials: M
authors.lastname: Han
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koyama
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazono
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage*; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010190:Pancreatic Neoplasms / Q000628:therapy*; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D008823:Micelles; C539404:PAsp(DET); D010455:Peptides; D011108:Polymers; D018125:Receptors, Transforming Growth Factor beta; D011107:Polylysine; D011092:Polyethylene Glycols; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I
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