Background: Metal oxides in nanoparticle form such as zinc oxide and titanium dioxide now appear on the
ingredient lists of household products as common and diverse as cosmetics, sunscreens, toothpaste, and medicine.
Previous studies of zinc oxide and titanium dioxide in non-nanoparticle format using animals have found few
adverse effects. This has led the FDA to classify zinc oxide as GRAS (generally recognized as safe) for use as a food
additive. However, there is no regulation specific for the use of these chemicals in nanoparticle format. Recent
studies, however, have begun to raise concerns over the pervasive use of these compounds in nanoparticle forms.
Unfortunately, there is a lack of easily-adaptable screening methods that would allow for the detection of their
biological effects.
Results: We adapted two image-based assays, a fluorescence resonance energy transfer-based caspase activation
assay and a green fluorescent protein coupled-LC3 assay, to test for the biological effects of different nanoparticles
in a high-throughput format. We show that zinc oxide nanoparticles are cytotoxic. We also show that titanium
dioxide nanoparticles are highly effective in inducing autophagy, a cellular disposal mechanism that is often
activated when the cell is under stress.
Conclusion: We suggest that these image-based assays provide a method of screening for the biological effects of
similar compounds that is both efficient and sensitive as well as do not involve the use of animals.
Background: Metal oxides in nanoparticle form such as zinc oxide and titanium dioxide now appear on the
ingredient lists of household products as common and diverse as cosmetics, sunscreens, toothpaste, and medicine.
Previous studies of zinc oxide and titanium dioxide in non-nanoparticle format using animals have found few
adverse effects. This has led the FDA to classify zinc oxide as GRAS (generally recognized as safe) for use as a food
additive. However, there is no regulation specific for the use of these chemicals in nanoparticle format. Recent
studies, however, have begun to raise concerns over the pervasive use of these compounds in nanoparticle forms.
Unfortunately, there is a lack of easily-adaptable screening methods that would allow for the detection of their
biological effects.
Results: We adapted two image-based assays, a fluorescence resonance energy transfer-based caspase activation
assay and a green fluorescent protein coupled-LC3 assay, to test for the biological effects of different nanoparticles
in a high-throughput format. We show that zinc oxide nanoparticles are cytotoxic. We also show that titanium
dioxide nanoparticles are highly effective in inducing autophagy, a cellular disposal mechanism that is often
activated when the cell is under stress.
Conclusion: We suggest that these image-based assays provide a method of screening for the biological effects of
similar compounds that is both efficient and sensitive as well as do not involve the use of animals.
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