Novel nanoformulation of disulfiram with bacterially synthesized copper oxide nanoparticles for augmenting anticancer activity: an in vitro study

Abstract

Background: Disulfiram (DS), in the presence of copper (Cu), exhibited potent broad anticancer activity. However, its clinical application is limited due to the poor solubility and stability. Hence, a novel nanocombination of DS with bacterially synthesized copper oxide nanoparticles (CuO NPs) was prepared herein to improve the anticancer efficacy of the typical DS–Cu complex. Our design utilized the nanocharacterization and prooxidant effect-mediated anticancer activity of CuO NPs which may lead to enhanced cellular uptake and thus improved anticancer efficacy of this unique nanocomplex. Results: The characterized DS–CuO NPs exhibited high stability in serum and the strongest selective anticancer activity, with the lowest half-maximum inhibitory concentration (IC50 < 15 nM), against human breast, lung and liver cancer cells, by >10-fold, compared to DS–Cu, CuO NPs and Cu. Importantly, DS–CuO NPs revealed better synergistic anticancer effect and higher cellular uptake than DS–Cu. Moreover, this novel nanocomplex showed higher prooxidant effect-mediated apoptosis and anti-metastatic potential. This was accomplished by elevating cellular reactive species content with inhibiting the antioxidant defenders (functional marker of cancer stem cells (aldehyde dehydrogenase) and nuclear factor erythroid 2-related factor2), matrix metallopeptidase 9 and NF-κB as well as enhancing p53 expression. Conclusion: All of the aforementioned findings verified that this novel nanocomplex was capable of improving the therapeutic index of the conventional DS–Cu complex. The potent selective anticancer activity of this promising nanomedicine merits further investigation, as a separate future study, using animal models as preliminary step before its clinical application. Graphic abstract: [Figure not available: see fulltext.]