Combined Delivery of a Lipopolysaccharide-Binding Peptide and the Heme Oxygenase-1 Gene Using Deoxycholic Acid-Conjugated Polyethylenimine for the Treatment of Acute Lung Injury
- Authors
- Kim, Ji Yeon; Piao, Chunxian; Kim, Gyeungyun; Lee, Seonyeong; Lee, Min Sang; Jeong, Ji Hoon; Lee, Minhyung
- Issue Date
- Aug-2017
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- acute lung injury; anti-inflammation; gene delivery; heme oxygenase-1; lipopolysaccharide-binding peptide
- Citation
- MACROMOLECULAR BIOSCIENCE, v.17, no.8
- Indexed
- SCIE
SCOPUS
- Journal Title
- MACROMOLECULAR BIOSCIENCE
- Volume
- 17
- Number
- 8
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/5387
- DOI
- 10.1002/mabi.201600490
- ISSN
- 1616-5187
- Abstract
- A ternary complex comprising plasmid DNA, lipopolysaccharide-binding peptide (LBP), and deoxycholic acid-conjugated polyethylenimine (PEI-DA) is prepared for combinational therapy of acute lung injury (ALI). The LBP is designed as an anti-inflammatory peptide based on the lipopolysaccharide (LPS)-binding domain of HMGB-1. In vitro cytokine assays show that LBP reduces levels of proinflammatory cytokines by inhibiting LPS. PEI-DA is synthesized as the gene carrier by conjugation of deoxycholic acid to low-molecular weight polyethy-lenimine (2 kDa, PEI2k). PEI-DA has higher transfection efficiency than high-molecular weight polyethylenimine (25 kDa, PEI25k). The ternary complex of an HO-1 plasmid (pHO-1), PEI-DA, and LBP is prepared as a combinational system to deliver the therapeutic gene and peptide. The transfection efficiency of the ternary complex is higher than that of the pHO-1/PEI-DA binary complex. The ternary complex also reduces TNF-alpha secretion in LPS-activated Raw264.7 macrophage cells. Administration of the ternary complex into the lungs of an animal ALI model by intratracheal injection induces HO-1 expression and reduces levels of proinflammatory cytokines more efficiently than the pHO-1/PEI-DA binary complex or LBP alone. In addition, the ternary complex reduces inflammation in the lungs. Therefore, the pHO-1/PEI-DA/LBP ternary complex may be an effective treatment for ALI.
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