Amelioration of cirrhotic portal hypertension by targeted cyclooxygenase-1 siRNA delivery to liver sinusoidal endothelium with polyethylenimine grafted hyaluronic acid

In this study, hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for the targeted delivery of COX-1 siRNA to LSECs. Compared to non-targeted PEI, HA-PEI mediated much more efficient siRNA delivery, which resulted in potent targeted gene silencing in LSECs. In vivo, HA-PEI notably increased the accumulation of siRNA along the sinusoidal lining of the liver, inhibited over-activation of the COX-1/TXA2 pathway in LSECs, and successfully reduced portal pressure in cirrhotic mice. These results highlight the potential of HA-PEI complexed siRNA to serve as a LSECs-specific nanomedical system for effective gene therapy in PH. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research