How Does the Cell Overcome LCP Nanoparticle-Induced Calcium Toxicity?

To address the question of how cells respond to the possible Ca2+ toxicity caused by the release of Ca2+ into the cytoplasm by LCP nanoparticles, a series of in vitro and in vivo studies using Ca2+ pump inhibitors were conducted. The results indicated that two major Ca2+ pumps on the plasma membrane and the mitochondrial membrane, respectively, were able to rapidly respond to the elevated cytosolic Ca2+ concentration and prevent Ca2+-induced apoptosis or necrosis. However, exposure to specific inhibitors of calcium pumps would cause LCP-treated H460 cells to undergo necrosis both in vitro and in vivo. These results demonstrated that the Ca2+ delivered by LCP was not toxic to cells when the cells contain functional Ca2+ pumps.