title: Anticancer effect of gene/peptide co-delivery system using transferrin-grafted LMWSC.
abstract: A series of ternary complex was designed to deliver psiRNA-bcl2 and (KLA)4 peptide into cancer cells for cancer therapy. The delivered psiRNA-bcl2 induced gene-silencing in a nucleus of cancer cells, while (KLA)4 peptide inhibited cancer growth via mitochondrial apoptosis, indicating that the ternary complexes exerted very strong synergistic effects on cancer growth suppression by acting on psiRNA-bcl2 and (KLA)4 peptide simultaneously. The ternary complexes having a targeting-ligand, transferrin (TfP), were found to be especially effective at binding to the TfP receptor rich cancer cells, HCT119. The plasmid DNA (pDNA) in ternary complexes was completely condensed at various content of LMWSC-PEG-TfP (32-64 times more than pDNA) and released into cells. pDNA in the complexes was protected from DNase present on the exterior of cells. The size (165-248 nm) of ternary complexes with LMWSC-PEG-TfP was increased, but surface charges (3-4.5 mV) were decreased. These results likely occurred because the free amine-group of LMWSC decreased in response to conjugated transferrin. Moreover, transfected ternary complexes with LMWSC-PEG-TfP were not expressed in the normal cells (HEK293), but were over expressed in HCT119 cells. These findings indicate that the ternary complexes can be specifically targeted to HCT119 cancer cells. The useful complexes for gene and peptide delivery had high anticancer activities via a synergistic effect due to co-operative action of psiRNA and (KLA)4 peptide in HCT119 cells.
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 540-742, Republic of Korea.
authors.forename: Gyeong-Won
authors.initials: GW
authors.lastname: Jeong
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 540-742, Republic of Korea.
authors.forename: Seong-Cheol
authors.initials: SC
authors.lastname: Park
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 540-742, Republic of Korea.
authors.forename: Changyong
authors.initials: C
authors.lastname: Choi
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 540-742, Republic of Korea.
authors.forename: Joung-Pyo
authors.initials: JP
authors.lastname: Nam
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 540-742, Republic of Korea.
authors.forename: Tae-Hun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Chemical and Biochemical Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Choi
authors.affiliation: CGbio Co. Ltd, Jangseong-gun 515-893, Republic of Korea.
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 540-742, Republic of Korea. Electronic address: jwnah@sunchon.ac.kr.
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D020868:Gene Silencing; D019254:Genes, bcl-2 / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000378:metabolism*; D050801:Ternary Complex Factors / Q000737:chemistry*; D014162:Transfection / Q000379:methods*; D014168:Transferrin / Q000737:chemistry*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C535058:KLA peptide; D010455:Peptides; D050801:Ternary Complex Factors; D014168:Transferrin; D048271:Chitosan
keywords: (KLA)(4) peptide; LMWSC; Ternary complex; Transferrin; psiRNA-BCL2