Docetaxel-carboxymethylcellulose nanoparticles ameliorate CCl 4 -induced hepatic fibrosis in mice

摘要

Chronic liver diseases have recently garnered substantial attention as a leading cause of death around the world. During the progression of liver fibrosis/cirrhosis induced by chronic liver injury, hepatic stellate cells (HSCs) play key roles in the regulation of liver fibrogenesis and can even accelerate the progression of hepatocellular carcinoma (HCC). Thus, inhibition of HSC activation or suppression of inflammatory cytokine secretion by HSCs may be an efficient therapeutic strategy to ameliorate liver fibrosis/cirrhosis. In this study, we demonstrated that Cellax NPs (Carboxymethylcellulose ? docetaxel-conjugated nanoparticles), which are nanoscale Pegylated carboxymethylcellulose ? DTX conjugates, selectively target activated HSCs and abrogate their fibrogenic properties in vitro. Furthermore, Cellax NPs alleviated CCl 4 -induced hepatic fibrosis and suppressed HCC progression in a clinically relevant HCC model associated with underlying liver fibrosis in vivo. Taken together, Cellax NPs demonstrate great therapeutic promise as a treatment for liver fibrosis and cancer. ? 2017 Informa UK Limited, trading as Taylor & Francis Group.