title: Target gene delivery from targeting ligand conjugated chitosan-PEI copolymer for cancer therapy.
abstract: 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.
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea. Electronic address: alwaysshh@sunchon.ac.kr.
authors.forename: Joung-Pyo
authors.initials: JP
authors.lastname: Nam
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea. Electronic address: jwnah@sunchon.ac.kr.
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D010957:Plasmids; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D048271:Chitosan; D004247:DNA; D011094:Polyethyleneimine; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C504164:O-carboxymethylchitosan; C508053:ERBB2 protein, human
keywords: Gene delivery carrier; Gene therapy; Polysaccharide; siRNA