Safety assessment of graphene oxide and microcystin-LR complex: a toxicological scenario beyond physical mixture

Abstract

Background: Nanomaterials have been widely used in electrochemistry, sensors, medicine among others applications, causing its inevitable environmental exposure. A raising question is the “carrier” effect due to unique surface properties of nanomaterials, which may collectively impact the bioavailability, toxicokinetic, distribution and biological effects of classic toxicants. Noteworthy, this aspect of information remains largely unexplored. Methods: Here, we deliberately selected two entities to mimic this scenario. One is graphene oxide (GO), which is made in ton quantity with huge surface-area that provides hydrophilicity and π–π interaction to certain chemicals of unique structures. The other is Microcystin-LR (MCLR), a representative double-bond rich liver-toxic endotoxin widely distributed in aquatic-system. Firstly, the adsorption of GO and MCLR after meeting under environmental conditions was explored, and then we focused on the toxicological effect and related mechanism of GO-MCLR complex on human skin cutin forming cells (HaCaT cells) and normal liver cells (L02 cells). Results: Abiotically, our study demonstrated that GO could effectively adsorb MCLR through hydrogen bonding and π–π interaction, the oxidation degree of GO-MCLR decreased significantly and surface defect level raised. Compared to GO or MCLR, GO-MCLR was found to induce more remarkable apoptosis and ferroptosis in both HaCaT and L02 cells. The underlying mechanism was that GO-MCLR induced stronger intracellular reactive oxygen species (ROS) and mtROS generation, followed by Fe2+ accumulation, mitochondrial dysfunction and cytoskeletal damage. Conclusions: These results suggest that the GO-MCLR complex formed by GO adsorption of MCLR may exhibit more toxic effects than the single material, which demonstrates the necessity for assessing nano-toxicant complexity. Our discovery may serve as a new toxicological paradigm in which nanomaterial mediated surface adsorption effects could impact the degree of cytotoxicity and toxicological mechanisms of classic toxins. Graphical Abstract: [Figure not available: see fulltext.]