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Combined delivery of HMGB-1 box A peptide and S1PLyase siRNA in animal models of acute lung injury

Title
Combined delivery of HMGB-1 box A peptide and S1PLyase siRNA in animal models of acute lung injury
Author
이민형
Keywords
Acute lung injury; Combined delivery; High mobility group box-1 A peptide; Sphingosine-1-phosphate lyase; siRNA
Issue Date
2014-02
Publisher
ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Citation
Journal of Controlled Release, Vol.175 No.- [2014], 25p ~ 35p
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 nontoxic. The siS1PLyase/HMGB1A/R3V6 complex reduced the levels of IL-6 and TNF-alpha 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. (C) 2013 Elsevier B.V. All rights reserved.S1Plyase 시르나 (siS1PLyase)와 재조합형 고이동성 그룹 box-1을 가진 결합 요법은 펩티드 (HMGB1A)를 권투하고 급성 폐 손상 (알리)의 처리를 위한 시너지 효과를 가질 수 있다. 효율적인 전달을 위해, R3V6 펩티드는 캐리어로서 사용되었다. siS1PLyase와 HMGB1A와 R3V6의 삼원 복합체는 전하 상호작용에 의해 생산되었다. siS1PLyase/HMGB1A/R3V6 삼원 복합체는 폴리에틸렌이민 보다 더 효율적으로 LA-4 허파 상피성 세포로의 시르나에게 (PEI)와 리포펙타민을 전했다. 게다가, 삼원 복합체는 논-톡식. siS1PLyase/HMGB1A/R3V6 콤플렉스는 IL-6과 TNF-&alpha의 레벨을 감소시켰다; 단지 HMGB1A 또는 LPS 활성 대식 세포 셀에서 siS1PLyase/R3V6 콤플렉스 보다 더 효율적으로. siS1PLyase/HMGB1A/R3V6 콤플렉스의 생체내의 관리는 효율적으로 S1PLyase 레벨을 LPS 유도 알리 모델에서 감소시켰다. 게다가, 콤플렉스는 염증성 응답과 아폽토시스를 알리 모델에서 감소시켰다. 결론적으로, siS1PLyase와 HMGB1A는 알리의 처리를 위해 상승적 치료 효과를 가진다. 게다가, R3V6은 siS1PLyase와 HMGB1A의 결합된 송출을 위한 효율적 캐리어이다.
URI
http://www.sciencedirect.com/science/article/pii/S0168365913009504http://hdl.handle.net/20.500.11754/49306
ISSN
0168-3659; 1873-4995
DOI
10.1016/j.jconrel.2013.12.008
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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