title: Combined delivery of HMGB-1 box A peptide and S1PLyase siRNA in animal models of acute lung injury.
abstract: The combinational therapy with S1Plyase siRNA (siS1PLyase) and recombinant high mobility group box-1 box A peptide (HMGB1A) may have a synergistic effect for the treatment of acute lung injury (ALI). For efficient delivery, the R3V6 peptides were used as a carrier. The ternary complex of siS1PLyase, HMGB1A, and R3V6 was produced by charge interaction. The siS1PLyase/HMGB1A/R3V6 ternary complex delivered siRNA into the LA-4 lung epithelial cells more efficiently than polyethylenimine (PEI) and Lipofectamine. Furthermore, the ternary complex was non-toxic. The siS1PLyase/HMGB1A/R3V6 complex reduced the levels of IL-6 and TNF-α more efficiently than HMGB1A only or siS1PLyase/R3V6 complex in the LPS activated macrophage cells. In vivo administration of the siS1PLyase/HMGB1A/R3V6 complex reduced the S1PLyase level efficiently in an LPS-induced ALI model. Furthermore, the complex reduced the inflammatory response and apoptosis in the ALI model. In conclusion, siS1PLyase and HMGB1A have a synergistic therapeutic effect for the treatment of ALI. Furthermore, R3V6 is an efficient carrier for combined delivery of siS1PLyase and HMGB1A.
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791Republic of Korea.
authors.forename: Binna
authors.initials: B
authors.lastname: Oh
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791Republic of Korea. Electronic address: minhyung@hanyang.ac.kr.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000446:Aldehyde-Lyases / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry; D024243:HMGB1 Protein / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D004337:Drug Carriers; D024243:HMGB1 Protein; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000446:Aldehyde-Lyases; C022649:sphingosine 1-phosphate lyase (aldolase)
keywords: Acute lung injury; Combined delivery; High mobility group box-1 A peptide; Sphingosine-1-phosphate lyase; siRNA