Docetaxel-carboxymethylcellulose nanoparticles ameliorate CCl 4 -induced hepatic fibrosis in mice
Journal
Journal of Drug Targeting
Journal Volume
26
Journal Issue
44322
Pages
516-524
Date Issued
2018
Author(s)
Chih-Chun Chang
Yang Yang
Dong-Yu Gao
Bryan Hoang
Po-Han Chao
Ling-Hsuan Chen
Joseph Bteich
Tsaiyu Chiang
Jia-Yu Liu
Shyh-Dar Li
Yunching Chen
Abstract
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.
SDGs
Other Subjects
antifibrotic agent; antineoplastic agent; carboxymethylcellulose; carboxymethylcellulose docetaxel conjugated nanoparticle; collagen type 1; messenger RNA; nanoparticle; osteonectin; paclitaxel; serum albumin; unclassified drug; antineoplastic agent; carbon tetrachloride; carboxymethylcellulose; docetaxel; drug carrier; macrogol; nanoparticle; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; Article; cancer growth; carbon tetrachloride-induced liver fibrosis; cell differentiation; cell viability; conjugate; controlled study; drug efficacy; drug protein binding; drug synthesis; fibroblast; human; human cell; in vitro study; liver cell carcinoma; liver tissue; male; mouse; mRNA expression level; nonhuman; priority journal; protein expression level; tumor associated leukocyte; tumor microenvironment; upregulation; animal; C3H mouse; chemistry; complication; disease exacerbation; disease model; drug effect; hepatic stellate cell; liver cell carcinoma; liver cirrhosis; liver tumor; pathology; Animals; Antineoplastic Agents; Carbon Tetrachloride; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; Disease Models, Animal; Disease Progression; Docetaxel; Drug Carriers; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Mice; Mice, Inbred C3H; Nanoparticles; Polyethylene Glycols
Publisher
Taylor and Francis Ltd
Type
journal article