Dexamethasone-loaded peptide micelles for delivery of the heme oxygenase-1 gene to ischemic brain
- Authors
- Lee, Jiyoung; Hyun, Hyesun; Kim, Jinyoung; Ryu, Jae Hwan; Kim, Hyun Ah; Park, Ji Hwan; Lee, Minhyung
- Issue Date
- Feb-2012
- Publisher
- ELSEVIER
- Keywords
- Gene delivery; Gene therapy; Peptide; Micelle; Stroke
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.158, no.1, pp.131 - 138
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 158
- Number
- 1
- Start Page
- 131
- End Page
- 138
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/166404
- DOI
- 10.1016/j.jconrel.2011.11.001
- ISSN
- 0168-3659
- 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 1 hr 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, p beta-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.
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