title: Construction of a tumor cell-targeting non-viral gene delivery vector with polyethylenimine modified with RGD sequence-containing peptide.
abstract: The objective of the present study was to construct a novel type of non-viral gene delivery vector with high delivery efficiency and specific tumor cell-targeting ability. The CP9 peptide (CYGGRGDTP) containing Arg-Gly-Asp sequence was employed to be conjugated onto polyethylenimine (PEI) to act as the role of the targeting moiety. The chemical linker, N-succinimidyl-3-(2-pyridyldithio) propionate, was applied during the synthesis of the vector (CP9-PEI). The physicochemical characteristics of the vector were evaluated by the methods of1H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, gel retardation assay, electron microscope observation and particle size detection. HepG2 cells were used to verify the gene delivery efficiency and targeting ability by gene delivery procedure and free CP9 peptide inhibition tests. The results showed that the successful synthesis of CP9-PEI and the synthesized vector may efficiently condense plasmid DNA into round particles with diameters of ~200 nm at a polymer/pDNA ratio of 10. CP9-PEI may deliver the reporter gene into HepG2 cells with higher efficiency and the efficiency may be inhibited by the free CP9 peptide. The present study suggested that the modification of PEI with the CP9 peptide is an effective method to construct a novel tumor cell-targeting non-viral vector, and that the novel vector exhibits great prospect in the field of cancer gene therapy.
authors.affiliation: Department of Intensive Care Unit, Xiasha Hospital, Hangzhou, Zhejiang 310019, P.R. China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Xing
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Pan
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Intensive Care Unit, Xiasha Hospital, Hangzhou, Zhejiang 310019, P.R. China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: DA
authors.initials: D
authors.lastname: Li
keywords: gene delivery; integrin; non-viral vector; polyethylenimine