title: Enhanced tumor-targeted gene delivery by bioreducible polyethylenimine tethering EGFR divalent ligands.
abstract: This work demonstrates successful delivery of a gene to EGFR-overexpressed cancer cells by using a rationally designed branched GE11 peptide as a targeting ligand. In addition, we exploited the effect of the divalent structure of the branched GE11 peptide on the gene delivery and tumor targeting efficiency, compared to the monovalent GE11 peptide. The GE11 or branched GE11-tethered polymers were successfully synthesized. They are composed of a targeting peptide, disulfide crosslinked low molecular weight polyethylenimine and polyethylene glycol. Here, we evaluated the physicochemical properties, cytotoxicity and in vitro transfection efficiency and in vivo biodistribution of the GE11 and branched GE11 tethered polyplexes. Our results demonstrated that GE11 and bGE11-tethered gene delivery carriers showed efficient gene condensing ability, an enhanced transfection efficiency and targeting ability with low cytotoxicity. Interestingly, the branched GE11-tethered polymer showed the greater targeting ability to EGFR-overexpressed cancer cells in vivo than the GE11-tethered polymer. Therefore, this branched structure of targeting ligand has the potential for providing a novel strategy to design an efficient targeted delivery system.
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science and Department of Chemistry, Pohang University of Science and Technology (POSTECH) 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea. wjkim@postech.ac.kr.
authors.forename: Duhwan
authors.initials: D
authors.lastname: Lee
authors.forename: Yeong Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.forename: Myung Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers
chemical_list: C572557:GE11 peptide; D008024:Ligands; D010455:Peptides; D011108:Polymers; D011092:Polyethylene Glycols; D011094:Polyethyleneimine