Inverse relationship between elemental selenium nanoparticle size and inhibition of cancer cell growth in vitro and in vivo

Elemental selenium nanoparticles (SeNPs) have been demonstrated to be equivalent to selenomethionine and methylselenocysteine in upregulating selenoenzymes; however, the toxicity of SeNPs is markedly lower than these two organic selenium compounds. The objective of this study was to determine the effect of SeNP size on cancer cell growth and ascertain whether production of reactive oxygen species (ROS) is implicated as a candidate mechanism of action. Two types of SeNPs (averaging 35 nm and 91 nm) were investigated. Cell accumulation was inhibited in vitro and in vivo in a manner inversely proportional to particle size. In vitro modeling experiments showed the reduction of SeNPs to be glutathione concentration dependent and to result in ROS formation. Both SeNP biotransformation and ROS production were size dependent, with the smaller SeNPs being more active, thereby suggesting that small-sized SeNPs are more effective in inhibiting cancer cell proliferation through an ROS mediated mechanism.