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

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Sakpakdeejaroen, Intouch and Somani, Sukrut and Laskar, Partha and Irving, Craig and Mullin, Margaret and Dufes, Christine (2020) Anti-tumor activity of intravenously administered plumbagin entrapped in targeted nanoparticles. Journal of Biomedical Nanotechnology, 16 (1). pp. 85-100. ISSN 1550-7033 (https://doi.org/10.1166/jbn.2020.2874)

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Abstract

Plumbagin, a natural naphthoquinone 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 solubility in water and rapid elimination following in vivo administration 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 types of cancer cells, could lead to a selective delivery of the drug to tumors following intravenous administration and enhance its chemotherapeutic effects. The objectives of this study were therefore to prepare and characterize transferrin-conjugated, PEGylated PLGA nanoparticles entrapping plumbagin, and to assess their anti-cancer efficacy in vitro as well as in tumor-bearing mice. The intravenous administration of transferrin-conjugated PEGylated PLGA nanoparticles resulted in 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.

ORCID iDs

Sakpakdeejaroen, Intouch ORCID logoORCID: https://orcid.org/0000-0002-5045-7581, Somani, Sukrut ORCID logoORCID: https://orcid.org/0000-0002-0697-1110, Laskar, Partha, Irving, Craig, Mullin, Margaret and Dufes, Christine ORCID logoORCID: https://orcid.org/0000-0002-7963-6364;
CORE (COnnecting REpositories)