Decorating protein nanospheres with lactoferrin enhances oral COX-2 inhibitor/herbal therapy of hepatocellular carcinoma

: Lactoferrin (LF)-targeted gliadin nanoparticles (GL-NPs) were developed for targeted oral therapy of hepatocellular carcinoma. : Celecoxib and diosmin were incorporated in the hydrophobic matrix of GL-NPs whose surface was decorated with LF by electrostatic interaction for binding to asialoglycoprotein receptors overexpressed by liver cancer cells. : Targeted GL-NPs showed enhanced cytotoxic activity and increased cellular uptake in liver tumor cells compared with nontargeted NPs. Moreover, they demonstrated superior antitumor effects including reduction in the expression levels of tumor biomarkers and induction of caspase-mediated apoptosis. imaging of isolated organs exhibited extensive accumulation of NPs in livers more than other organs. : LF-targeted GL-NPs could be considered as an efficient nanoplatform for targeted oral drug delivery for liver cancer therapy.