Novel nanoformulated diethyldithiocarbamate complexes with biosynthesized or green chemosynthesized copper oxide nanoparticles: An in vitro comparative anticancer study

Int J Pharm. 2021 Nov 20:609:121149. doi: 10.1016/j.ijpharm.2021.121149. Epub 2021 Sep 30.

Abstract

Developing more soluble and stable nanoformulation for the potent anticancer complex of copper diethyldithiocarbamate (CD) is extremely desired. Herein, for the first time, CD nanoparticles (NPs) were formulated by chelating diethyldithiocarbamate to bacterially and green chemically prepared copper oxide NPs (Bio CO NPs and Chemo CO NPs, respectively). Chemo CO NPs were produced in simpler and less time-consuming manner with higher NPs homogeneity. These CO NPs were identified, by X-ray diffractometer, as CuO and Cu2O, respectively. The nanoformulated CD complexes (Bio CD NPs and Chemo CD NPs) which have nanosizes (215.7 nm and 148.1 nm, respectively) with negative zeta potentials (∼-20 mv), exhibited not only high serum stability and solubility but also a potent anticancer effect. More importantly, Chemo CD NPs outperformed Bio CD NPs in the terms of synergistic anticancer index, apoptosis induction (>81% and <54%, respectively) and anti-migration efficacy (≥80% and <71%, respectively). This could be attributed to smaller nanosize and Cu2O of Chemo CD NPs causing higher cellular uptake with stronger inhibition of aldehyde dehydrogenase 1A1 and more free radical generation in Chemo CD NPs-treated cancer cells than Bio CD NPs. This distinct anticancer efficacy of novel Chemo CD NPs deserves further investigation using animal models.

Keywords: Anti-cancer cell migration; Apoptosis-dependent anticancer efficacy; Biosynthesized cupric oxide nanoparticles; Cellular redox status; Diethyldithiocarbamate nanocomplexes; Green chemosynthesized cuprous oxide nanoparticles.

MeSH terms

  • Animals
  • Cell Death
  • Copper
  • Ditiocarb
  • Metal Nanoparticles*
  • Nanoparticles*
  • Oxides

Substances

  • Oxides
  • Copper
  • Ditiocarb