title: Homo-catiomer integration into PEGylated polyplex micelle from block-catiomer for systemic anti-angiogenic gene therapy for fibrotic pancreatic tumors.
abstract: Homo-poly{N'-[N-(2-aminoethyl)-2-aminoehtyl]aspartamide} [PAsp(DET), H] 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.
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Qixian
authors.initials: Q
authors.lastname: Chen
authors.forename: Kensuke
authors.initials: K
authors.lastname: Osada
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ishii
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchida
authors.forename: Theofilus A
authors.initials: TA
authors.lastname: Tockary
authors.forename: Taisuke
authors.initials: T
authors.lastname: Endo
authors.forename: Zhishen
authors.initials: Z
authors.lastname: Ge
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kinoh
authors.forename: Mitsunobu R
authors.initials: MR
authors.lastname: Kano
authors.forename: Keiji
authors.initials: K
authors.lastname: Itaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D008823:Micelles; D011092:Polyethylene Glycols