Sequential exposures of single walled carbon nanotubes and heavy metal ions to macrophages induce different cytotoxicity

The probability of occupational exposure rises with the increasing production and biomedical application of carbon nanotubes (CNTs). Thus, the risk of co-exposure of nanomaterials with environmental pollutants is also increasing. Although many studies have focused on the combined toxicity of nanomaterials and pollutants, more attention has been paid to the toxicity of nanomaterials after adsorbing pollutants or the toxicity of nanomaterials and pollutants exposed simultaneously. Few studies have been conducted on the toxicity and toxicity mechanisms of nanomaterials and environmental pollutants following sequential exposure. In this study, we employed THP-1 cells to investigate how pristine single walled CNTs (p-SWCNTs) and oxidized single walled CNTs (SWCNT-COOHs) pretreatments at a non-lethal dose of 10 μg/mL affect cell responses to metal ions (i. e., Pb²⁺, Cu²⁺, and Cr(VI)). We found that p-SWCNTs caused more significant damage to cell membrane integrity than SWCNT-COOHs, which led to higher metallothionein (MT) levels and increased transport of metal ions into cells. Pretreatment of p-SWCNTs in cells significantly increased the cytotoxicity of Pb²⁺, Cu²⁺, and Cr(VI) by 2-4-fold, whereas SWCNT-COOHs pretreated cells showed no noteworthy changes in response to heavy metals, which were further confirmed by the cellular Reactive Oxygen Species (ROS) assays. These findings indicate that understanding the effects of the exposure sequence of engineered nanomaterials and environmental pollutants on their toxicity provides an excellent complement to combined toxicity evaluation.

Cytotoxicity; Metal ions; Oxidative stress; Sequential exposure; Single-walled carbon nanotubes (SWCNTs).