Thus far, tremendous efforts have been made to understand the bio-safety of metal-based nanoparticles (MNPs). Nevertheless, most previous studies focused on specific adverse outcomes of MNPs at unrealistically high concentrations with little relevance to the National Institute for Occupational Safety and Health (NIOSH) exposure thresholds, and failed to comprehensively evaluate their toxicity profiles. To address these challenges, we here endeavored to multi-hierarchically profile the hazard effects of various popularly used MNPs in macrophages under low exposure doses. At these doses, no remarkable cell viability drop and cell death were induced. However, cellular anti-oxidant defense system was seen to be initiated in cells by all MNPs even at these low concentrations, albeit to a differential extent and through different pathways, as reflected by differential induction of the anti-oxidant enzymes and Nrf2 signaling. Regarding inflammation, rare earth oxide nanomaterials (REOs) except nCeO2 greatly increased IL-1β secretion in a NLRP3 inflammasome-dependent manner. By contrast, six REOs, AgNP-5nm, nFe2O3, nFe3O4 and nZnO were found to elevate TNF-α concentration through post-transcriptional regulation. Moreover, all MNPs except nCeO2 drastically altered cellular membrane/cytoskeleton meshwork, but leading to different outcomes, with condensed cellular size and reduced numbers of protrusions by REOs and elongated protrusions by other MNPs. Consequently, REOs (e.g. nDy2O3 and nSm2O3) impaired phagocytosis of macrophages, and other MNPs (such as AgNP-25nm and nZnO) reversely enhanced macrophagic phagocytosis. Alterations of membrane and cytoskeleton meshwork induced by these MNPs also caused disordered membrane potential and calcium ion flux. Collectively, our data profiled the biological effects of different MNPs in macrophages under low exposure doses, and deciphered a complex network that links multi-parallel pathways and processes to differential adverse outcomes.

Multi-hierarchically profiling the biological effects of various metal-based nanoparticles in macrophages under low-exposure doses

2019 Spring National Meeting

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