Therapeutic Effect of Sorafenib-Loaded TPGS-b-PCL Nanoparticles on Liver Cancer

Sorafenib has shown modest therapeutic effectiveness against hepatocellular carcinoma (HCC), but more effective therapies are needed. The objective of this research was to test the feasibility of using sorafenib-loaded polymer nanoparticles (NP-SFB) to enhance effectiveness against the tumor. Biodegradable d-alpha-tocopherol polyethylene glycol 1000 succinatepolycaprolactone (TPGS-b-PCL) nanoparticles were prepared by a modified nanoprecipitation method and tested for anti-tumor effect in HepG2 hepatoma cells and a HCC xenograft mouse model. The SFB-loaded TPGS-b-PCL nanoparticles had appropriate shape, mean particle size (122.3 nm), size distribution (determined with transmission electron microscopy and dynamic light scattering), stability, drug-release rate, and drug-loading content of an efficient drug-delivery vehicle. Compared with free SFB, the SFB-loaded TPGS-b-PCL NPs more effectively suppressed HepG2 cell growth, confirmed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, western blotting and flow cytometry analysis. Consistent with these in vitro studies, NP-SFB also more effectively delayed tumor growth in the HCC xenograft model than did free SFB (27 days vs. 20 days; P < 0.05). No adverse effect of NP-SFB treatment was observed. Therefore, the SFB-loaded TPGS-b-PCL NPs exhibited anti-HCC activity and safety that may make them candidates for trial in hepatoma therapy.