Regression of Melanoma Following Intravenous Injection of Plumbagin Entrapped in Transferrin-Conjugated, Lipid–Polymer Hybrid Nanoparticles

Intouch Sakpakdeejaroen,1 Sukrut Somani,1 Partha Laskar,1 Margaret Mullin,2 Christine Dufès1 1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK; 2College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UKCorrespondence: Christine DufèsStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, United KingdomTel +44 1415483796Fax +44 1415522562Email C.Dufes@strath.ac.ukBackground: Plumbagin, a naphthoquinone extracted from the officinal leadwort presenting promising anti-cancer properties, has its therapeutic potential limited by its inability to reach tumors in a specific way at a therapeutic concentration following systemic injection. The purpose of this study is to assess whether a novel tumor-targeted, lipid–polymer hybrid nanoparticle formulation of plumbagin would suppress the growth of B16-F10 melanoma in vitro and in vivo.Methods: Novel lipid–polymer hybrid nanoparticles entrapping plumbagin and conjugated with transferrin, whose receptors are present in abundance on many cancer cells, have been developed. Their cellular uptake, anti-proliferative and apoptosis efficacy were assessed on various cancer cell lines in vitro. Their therapeutic efficacy was evaluated in vivo after tail vein injection to mice bearing B16-F10 melanoma tumors.Results: The transferrin-bearing lipid–polymer hybrid nanoparticles loaded with plumbagin resulted in the disappearance of 40% of B16-F10 tumors and regression of 10% of the tumors following intravenous administration. They were well tolerated by the mice.Conclusion: These therapeutic effects, therefore, make transferrin-bearing lipid–polymer hybrid nanoparticles entrapping plumbagin a highly promising anti-cancer nanomedicine.Keywords: plumbagin, transferrin, tumor targeting, lipid–polymer hybrid nanoparticles, cancer therapy