Are metal oxide nanomaterials "toxic" without the cellular response?

What is it about?

When we talk about communicable diseases and illnesses, we often say that the symptoms are worse than the disease itself. For instance, when you are infected by influenza ("the flu"), the fever, sweating, dehydration, muscular weakness, and malaise that you suffer is your body (and your immune system's) way of removing the virus from yourself. Toxins are similar. When a cell attempts to neutralize a toxin, the biotransformation process generates a number of harmful molecules, including reactive oxygen species (e.g. superoxide, hydroxyl radical, etc.). These, and/or the biotransformed toxin, can sometimes be more damaging to cells than the original form of the toxin, or the parent toxin. In this study, we used blood plasma to simulate a rich biological environment of metabolites, proteins, lipids, and more. However, blood plasma in itself contains no blood cells- whether white or red- and therefore has no "living," responsive, adaptable components. When toxins are introduced to blood plasma, there is no response in the same way that a living cell would respond to a foreign particle, or virus, or bacterium.

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Why is it important?

Engineered nanomaterials (ENMs) are everywhere, and are only becoming more prevalent since the 2016 Nobel Prize in Chemistry was awarded for the development of molecular machines. ENMs are thus increasingly coming into contact with living cells- either deliberately (i.e. in their use as nanodrugs or nanomedicines) or indeliberately (i.e. being improperly disposed into the environment, and subsequently encountering living cells thereafter). Firstly, we wanted to see whether two common metal oxide nanospheres were toxic in themselves, or whether the cellular response to encountered ENMs "amplifies" their toxicity. Secondly, we wanted to determine whether blood plasma could serve as a viable test subject with which to assess the toxicity of ENMs.