title: Dexamethasone-loaded peptide micelles for delivery of the heme oxygenase-1 gene to ischemic brain.
abstract: The R3V6 peptides, which are composed of a 3-arginine block and a 6-valine block, formed self-assembled micelles in aqueous solution. Dye quenching assays showed that a hydrophobic fluorescent dye, 5-dodecanoylaminofluorescein (DAF), interacted with and was loaded into the hydrophobic core of the micelles. In this study, dexamethasone-loaded R3V6 peptide micelles (R3V6-Dexa) were evaluated as a gene carrier. R3V6-Dexa had higher gene delivery efficiency in human embryonic kidney 293 cells compared to those of the R3V6 peptides and poly-L-lysine (PLL). Dexamethasone might stabilize the micelle structure of the R3V6 peptides by forming strong hydrophobic cores and enhanced the transfection efficiency. Furthermore, R3V6-Dexa reduced the expression of an inflammatory cytokine, interleukin-6 (IL-6), more efficiently in lipopolysaccharide (LPS)-induced Raw264.7 cells than did dexamethasone, suggesting that R3V6-Dexa is also a useful carrier for dexamethasone delivery. A focal brain ischemia-reperfusion model was produced by middle cerebral artery occlusion (MCAO). A heme oxygenase-1 (HO-1) expression plasmid DNA, pSV-HO-1, was delivered into the brain using R3V6-Dexa as a carrier. The pSV-HO-1/R3V6-Dexa complex was injected into the brain 1hr prior to MCAO. Twenty-four hours later, the HO-1 expression of the pSV-HO-1/R3V6-Dexa injection group was higher than those of the MCAO control, pβ-Luc/R3V6-Dexa, and pSV-HO-1/PEI25k injection groups. In addition, the infarct size was reduced due to the delivery of pSV-HO-1/R3V6-Dexa complex. Therefore, R3V6-Dexa may be a useful carrier for HO-1 gene delivery and stroke gene therapy.
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Lee
authors.forename: Hyesun
authors.initials: H
authors.lastname: Hyun
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Ryu
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Ji Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D057809:HEK293 Cells; D051547:Heme Oxygenase-1 / Q000008:administration & dosage* / Q000235:genetics* / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008823:Micelles; D009842:Oligopeptides / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007166:Immunosuppressive Agents; D015850:Interleukin-6; D008823:Micelles; D009842:Oligopeptides; D003907:Dexamethasone; D051547:Heme Oxygenase-1