Given the novel physicochemical properties, graphene materials, such as graphene oxide (GO), are being developed for applications in various fields including biomedicine. Nonetheless, considerable knowledge gaps still exist regarding the understandings on GO’s environmental health and safety (EHS) impacts. Thus far, little attention has been paid to its secondary toxicity, synergistic effects and mal-adaption. Here, we show that GO at low concentrations (that did not directly incur significant cytotoxicity) can greatly enhance metal toxicity in macrophages by altering their cellular priming state. Specifically, GO caused impairments to cellular morphology and membrane integrity in macrophages, and remarkably enhanced cellular uptake of cadmium (Cd) and other non-essential metal ions (e.g. Hg and Gd). Furthermore, upon low-dose GO pre-treatment Cd at a non-toxic concentration brought about marked oxidative stress in macrophages and ultimately increased cell death. Mechanistic investigation illustrated that GO pre-treatment triggered cell death through apoptosis under Cd exposure. Overall, this study opens a new path to understand GO’s EHS impacts through a perspective of synergistic and secondary effects, a previously unidentified mechanism via which nanomaterials may pose detrimental effects on organisms.

Low-dose exposure of graphene oxide significantly increases metal toxicity to macrophages by altering their cellular priming state

256th National Meeting (2018)

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