Abstract
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-α-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.
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