Transferrin‐bearing liposomes entrapping plumbagin for targeted cancer therapy

The therapeutic potential of plumbagin, a naphthoquinone extracted from the officinal leadwort with anti-cancer properties, is hampered by its failure to specifically reach tumors at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use in clinic is further limited by its poor aqueous solubility, its spontaneous sublimation and rapid elimination in vivo. We hypothesize that the entrapment of plumbagin within liposomes grafted with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumors after intravenous administration. The objectives of this study were therefore to prepare and characterize transferrin-targeted liposomes entrapping plumbagin, and to evaluate their therapeutic efficacy in vitro and in vivo. The entrapment of plumbagin in transferrin-bearing liposomes led to an increase in plumbagin uptake by cancer cells, improved anti-proliferative efficacy and apoptosis activity in B16-F10, A431 and T98G cell lines compared to that observed with the drug solution. In vivo, the intravenous injection of transferrin-bearing liposomes entrapping plumbagin led to tumor suppression for 10% of B16-F10 tumors and tumor regression for a further 10% of the tumors. By contrast, all the tumors treated with plumbagin solution or left untreated were progressive. The animals did not show any signs of toxicity. Plumbagin entrapped in transferrin-bearing liposomes are therefore highly promising therapeutic systems that should be further optimized as a therapeutic tool for cancer treatment.