Biotinylated Epidermal Growth Factor Surface Modified Lipid Nanoparticles to Enhance the Targeting Efficiency in Liver Cancer Therapy

Hepatocellular carcinoma (HCC) or liver cancer is one of the most prevalent cancers with high morbidity rate worldwide. The aim of this study was to develop epidermal growth factor (EGF)surface modified solid lipid nanoparticles (SLN) to deliver doxorubicin (DOX) in the liver cancer model. The delivery system was characterized in terms of dynamic light scattering and physical parameters. Biological studies including cytotoxicity assay, cellular uptake, and in vivo anticancer efficacy study has been performed. EGF-receptor (EGFR) is over-expressed in a variety of tumor cells, and EGF is a known natural ligand of EGFR. The ability of the EGF to target the NPs to cancer cells that expressed different levels of EGFR was evaluated in vitro and in vivo. EGF conjugation remarkably increased the cellular uptake in EGF receptor overexpressing HepG2 and SMMC 7701 cell lines. Consistently, EGF-SLN-DOX showed enhanced cytotoxic effect than comparing to SLN-DOX in both the cancer cell lines owing to the ligand targeted receptor mediated-endocytosis. In vivo antitumor efficacy study showed a remarkable tumor regression profile for EGF conjugated delivery system and exhibited a significantly smaller tumor weight comparing to that of SLN-DOX and free DOX. To summarize, EGF-SLN-DOX was successfully developed and its superior performance has been proved by various in vitro and in vivo experiments. Put together, EGF-decorated NPs served as a potential therapeutic approach in the treatment of liver cancers.