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- Title
Targeted gene silencing of TLR4 using liposomal nanoparticles for preventing liver ischemia reperfusion injury.
- Authors
Jiang, N; Zhang, X; Zheng, X; Chen, D; Zhang, Y; Siu, L K S; Xin, H-B; Li, R; Zhao, H; Riordan, N; Ichim, T E; Quan, D; Jevnikar, A M; Chen, G; Min, W
- Abstract
RNAi-based therapy is a promising strategy for the prevention of ischemia-reperfusion injury (IRI). However, systemic administration of small interfering RNA (siRNA) may cause globally nonspecific targeting of all tissues, which impedes clinical use. Here we report a hepatocyte-specific delivery system for the treatment of liver IRI, using galactose-conjugated liposome nanoparticles (Gal-LipoNP). Heptocyte-specific targeting was validated by selective in vivo delivery as observed by increased Gal-LipoNP accumulation and gene silencing in the liver. Gal-LipoNP TLR4 siRNA treatment resulted in a significant decrease of serum alanine transferase (ALT) and aspartate transaminase (AST) in a hepatic IRI model. Histopathology displayed an overall reduction of the injury area in the Gal-LipoNP TLR4 siRNA treated mice. Additionally, neutrophil accumulation and lipid peroxidase-mediated tissue injury, detected by MPO, MDA and ROS respectively, were attenuated after Gal-LipoNP TLR4 siRNA treatment. Moreover, therapeutic effects of Gal-LipoNP TLR4 siRNA were associated with suppression of the inflammatory cytokines IL-1 and TNF-α. Taken together, this study is the first demonstration of liver IRI treatment using liver-specific siRNA delivery.
- Publication
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2011, Vol 11, Issue 9, p1835
- ISSN
1600-6143
- Publication type
Journal Article
- DOI
10.1111/j.1600-6143.2011.03660.x