To address the question of how cells respond to the possible Ca(2+) toxicity caused by the release of Ca(2+) into the cytoplasm by LCP nanoparticles, a series of in vitro and in vivo studies using Ca(2+) pump inhibitors were conducted. The results indicated that two major Ca(2+) pumps on the plasma membrane and the mitochondrial membrane, respectively, were able to rapidly respond to the elevated cytosolic Ca(2+) concentration and prevent Ca(2+)-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 Ca(2+) delivered by LCP was not toxic to cells when the cells contain functional Ca(2+) pumps.