Abstract
BackgroundDisulfiram (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.ResultsThe 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.ConclusionAll 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
Highlights
Disulfiram (DS), in the presence of copper (Cu), exhibited potent broad anticancer activity
In this current study, we exploited the chelating ability of DS to metal to prepare a novel nanoformulated complex with biologically synthesized CuO Copper oxide nanoparticles (NPs) using a simple and cheap method to improve the anticancer efficacy of a traditional DS complex. This novel crystalline needle-shaped complex (DS–CuO NPs) revealed acceptable nanocharacterization with good solubility and biostability in serum. This novel complex (DS–CuO NPs) exhibited better cellular uptake in breast, lung and liver cancer cell lines compared to DS–Cu
Previous studies found that CuO NPs had prooxidant activity-mediated potential anticancer effect by upregulating the expression of proapoptotic genes and downregulating oncogenes, whereas Cu alone did not show this activity
Summary
Disulfiram (DS), in the presence of copper (Cu), exhibited potent broad anticancer activity. Its clinical application is limited due to the poor solubil‐ ity and stability. A novel nanocombination of DS with bacterially synthesized copper oxide nanoparticles (CuO NPs) was prepared to improve the anticancer efficacy of the typical DS–Cu complex. Our design utilized the nanocharacteriza‐ tion and prooxidant effect-mediated anticancer activity of CuO NPs which may lead to enhanced cellular uptake and improved anticancer efficacy of this unique nanocomplex. Cancer is a leading cause of death and a major impediment to increasing life expectancy. Our current study focused on these cancer types. The efficacy of the current chemotherapeutic drugs is limited, in late-stage tumors. Repurposing approved drugs is a promising approach because it reduces risks with saving time and money, facilitating clinical translation
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