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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 vivodelivery 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.

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 vivodelivery 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.

Proc. Instn Ciu E m , Ciu Engng, 1995, 1 8 Nov., 180-185 0. Paper J0395/6 Debate: Contaminated sites are being over-engineered A. A. Wood, BEng, PhD, CEng, CGeol, FICE, FIStructE, FIWEM, FGS, and c. M. GrifFths, BSc, MSc, MInstWM, M M M ,MIEnvSc, FGS ~ ~~~~ D. L Barry, WSAtkins Environment The debate touched on the majority of key issues relating to contaminated land redevelopment and, to some degree, the increasingly more topical aspect of environmental liability...