Anti-tumor activity of intravenously administered plumbagin entrapped in targeted nanoparticles

Sakpakdeejaroen, Intouch and Somani, Sukrut and Laskar, Partha and Irving, Craig and Mullin, Margaret and Dufes, Christine (2019) Anti-tumor activity of intravenously administered plumbagin entrapped in targeted nanoparticles. Journal of Biomedical Nanotechnology. ISSN 1550-7033 (In Press)

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Plumbagin, a naphthoquinone extracted from the officinal leadwort, has recently been shown to exert promising anti-cancer effects. However, its therapeutic use is hampered by its failure to specifically reach tumors after intravenous administration, without secondary effects on normal tissues. Its poor aqueous solubility and rapid elimination in vivo further limit its potential use. We hypothesize that the entrapment of plumbagin within PEGylated PLGA nanoparticles conjugated with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumors following intravenous administration and enhance its chemotherapeutic effects. The objectives of this study were therefore to prepare and characterize transferrin-targeted, PEGylated PLGA nanoparticles entrapping plumbagin, and to evaluate their therapeutic efficacy in vitro and in vivo. The intravenous administration of transferrin-bearing PEGylated PLGA nanoparticles led to the complete suppression of 10% of B16-F10 tumors and regression of 30% of the tumors, with improvement of the animal survival compared to controls. The treatment was well tolerated by the animals. Transferrin-bearing PEGylated PLGA nanoparticles entrapping plumbagin are therefore highly promising therapeutic systems, able to lead to tumor regression and even suppression after intravenous administration without visible toxicity.