title: RPM peptide conjugated bioreducible polyethylenimine targeting invasive colon cancer.
abstract: CPIEDRPMC (RPM) peptide is a peptide that specifically targets invasive colorectal cancer, which is one of the leading causes of cancer-related deaths worldwide. In this study, we exploited RPM peptide as a targeting ligand to produce a novel and efficient gene delivery system that could potentially be used to treat invasive colon cancer. In order to achieve enhanced specificity to colon cancer cells, the RPM peptide was conjugated to a bioreducible gene carrier consisting of a reducible moiety of disulfide-crosslinked low molecular weight polyethylenimine, IR820 dye, and polyethylene glycol. Here, we examined the physiochemical properties, cytotoxicity, in vitro transfection efficiency, and in vivo biodistribution of the RPM-conjugated polyplex. Our results showed that the RPM-conjugated gene carrier formed a compact polyplex with pDNA that had low toxicity. Furthermore, the RPM-conjugated polymer not only had higher cellular uptake in invasive colon cancer than the non-targeted polymer, but also showed enhanced transfection efficiency in invasive colon cancer cells in vitro and in vivo.
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 790-784, Republic of Korea; Department of Chemistry Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Yeong Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 790-784, Republic of Korea; Department of Chemistry Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Duhwan
authors.initials: D
authors.lastname: Lee
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 790-784, Republic of Korea; Department of Chemistry Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Integrative Engineering, Chung-Ang University, Seoul 156-75l, Republic of Korea. Electronic address: heyshoo@cau.ac.kr.
authors.forename: Hansoo
authors.initials: H
authors.lastname: Park
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 790-784, Republic of Korea; Department of Chemistry Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea. Electronic address: wjkim@postech.ac.kr.
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004396:Coloring Agents / Q000737:chemistry / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007208:Indocyanine Green / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009690:Nucleic Acid Conformation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D010957:Plasmids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry*; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004396:Coloring Agents; C541053:IR 820; D009842:Oligopeptides; D010456:Peptides, Cyclic; C000604112:cysteinyl-prolyl-isoleucyl-glutamyl-aspartyl-arginyl-prolyl-methionyl-cysteine (1-9) disulfide; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D007208:Indocyanine Green
keywords: Bioreducible polymer; Colorectal cancer; Gene delivery; RPM peptide