Environmental Nanoparticles Endocytosis Causes the Influx of Calcium-Rich Extracellular Fluid and Calcium Overload

The understanding of the toxic effect of environmental nanoparticle exposure at the cellular level is critical. We surprisingly discovered that environmental nanoparticle endocytosis inadvertently transports a small volume of the surrounding extracellular fluid into the cells, without disruption of the cell membrane. Although the volume of engulfed fluid is relatively small, the corresponding Ca2+ influx is rather considerable. Nanoparticles, along with their “hijacked” extracellular fluid, accumulate in the lysosomes. Therefore, the elevated Ca2+ levels were observed in the lysosomes, accompanied by certain lysosomal damage. In contrast, inhibiting the influx of extracellular Ca2+ or activating the lysosomal calcium ion channel TRPML1 significantly mitigated lysosomal calcium overload. Overall, this study may be beneficial for nanoparticles-related ecotoxicological examination and risk assessment.