Target gene delivery from targeting ligand conjugated chitosan-PEI copolymer for cancer therapy.

Autor: Nam JP; Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea. Electronic address: alwaysshh@sunchon.ac.kr., Nah JW; Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea. Electronic address: jwnah@sunchon.ac.kr.
Jazyk: angličtina
Zdroj: Carbohydrate polymers [Carbohydr Polym] 2016 Jan 01; Vol. 135, pp. 153-61. Date of Electronic Publication: 2015 Aug 20.
DOI: 10.1016/j.carbpol.2015.08.053
Abstrakt: In this study, we designed a novel carrier which was having low cytotoxicity, site-specific target function, and high transfection efficiency using low molecular weight water soluble O-carboxymethyl chitosan (OCMCh), branched low molecular weight poly(ethyleneimine) (bPEI), and targeting ligand (epitope type, HER-2/neu). OCMCh/bPEI/targeting ligand, HPOCP copolymer, and targeting ligand-modified polyamphoteric polymer, and were prepared by chemical reaction and characterized by (1)H NMR and FT-IR. The binding affinity, protecting efficiency, and releasing ability of gene/HPOCP polyplex were confirmed by gel retardation assay. The pDNA(pEGFP)/HPOCP polyplexes showed high gene transfection efficiency in HCT 119 cell. In addition, siRNA/HPOCP polyplexes formed spherical shape and have particle sizes from 100 to 300nm. The siRNA/HPOCP polyplexes have lower cytotoxicity than PEI in the all of siRNA concentrations ranging from 0 to 2μg/μL in HEK 293 cells. The cell viability of siRNA/HPOCP polyplexes was performed in SK-Br3 cells with VEGF siRNA or BCL2 siRNA. In addition, confocal laser-scanning microscopy and flow cytometry assay were performed for cellular localization and cellular uptake efficiency of siRNA/HPOCP polyplexes. The results of the present study demonstrate that HPOCP copolymer is a good candidate as gene delivery carriers for gene delivery system or gene therapy.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE