Nano-fabrication using minute nano-particles (particles between 1 and 10,000 nanometers in size) offers the enticing promise of creating useful products. However, any technology can have unintended effects that must be addressed. Nano-particles are no exception. All substances have a toxic effect above a critical concentration. This includes silver nano-particles (AgNPs) which are toxic to living organisms at high enough concentrations. In order to protect workers and the public against potential toxins, it is important to understand why they are toxic. What is the basis of AgNP toxicity? Ask an insect.
Armstrong and colleagues* have used Drosophila (flies) to elucidate the mechanism of toxic effects observed for some AgNPs. Their initial study determined the relation between dose and toxic effects. Compared to Drosophila fed AgNP-free diet, Drosophila larvae fed on a diet containing 50 mg/l AgNPs survived, but lived less long. Interestingly, AgNPs in the diet (but not molecular silver) caused the cuticle to be lighter in color and not properly sclerotized. Was the lighter color of the cuticle a clue to the toxicity of AgNPs?
Yes. Insect cuticle darkens because of enzymes that require copper as a co-factor. The effect of AgNPs on cuticle darkening could be reversed by increasing the concentration of copper in the diet. Additional studies with Drosophila flies mutant for cellular copper transporters led Armstrong and colleagues to conclude that AgNPs can interfere with copper transport into cells. AgNPs are toxic to living organisms because they create a deficiency of copper. The protein portion of the enzymes are produced normally, but they are less active because the copper is not incorporated into the enzyme active site, possibly due to lack of copper availability.
What does this say about the toxicity of AgNPs? At least one of the effects is interference with copper regulation. Many enzymes in addition to the tyrosinase (responsible for darkening of insect cuticle) utilize copper and are affected by AgNPs. These include important detoxification enzymes that metabolize oxygen radicals created by normal biological processes. Organisms with decreased activity of copper-dependent detoxification enzymes suffer excess oxidative damage to their tissues, leading to their demise. Increased dietary copper is antidotal to these effects.
Studies such as this one are important in determining the risk of nano-particles and potential means of making them safer to humans. This is one more example of the usefulness of insects as model systems to study important biological and toxicological effects.
*Armstrong N, Ramamoorthy M, Lyon D, Jones K, Duttaroy A (2013) Mechanism of Silver Nanoparticles Action on Insect Pigmentation Reveals Intervention of Copper Homeostasis. PLoS ONE 8(1): e53186. doi:10.1371/journal.pone.0053186