A calcium hydroxide/oleic acid/phospholipid nanoparticle induced cancer cell apoptosis by the combination of intracellular calcium overload and lactic acidosis elimination

Abstract

Intracellular calcium ions (Ca²⁺) influence the proliferation–apoptosis balance, and lactic acidosis is an innate feature of a malignant tumor. In this study, a calcium hydroxide/oleic acid/phospholipid nanoparticle [CUR–Ca(OH)₂-OA/PL NP] with lipase/pH dual responsive delivery of Ca²⁺ and curcumin (CUR) was developed for inducing cancer cell apoptosis by a combination of intracellular calcium overload and lactic acidosis elimination. The nanoparticle showed a core–shell structure with some good performance, including an adequate nano-size, negative charge, good blood circulation stability, and non-hemolysis. MDA-MB-231 breast cancer cells exhibited a higher lipase activity than A549 human lung adenocarcinoma cells and L929 mouse fibroblasts by fluorescence analysis. CUR–Ca(OH)₂-OA/PL NPs were highly internalized by MDA-MB-231 cells, intracellularly released CUR and Ca²⁺, triggered the activation of caspase 3 and caspase 9, and caused apoptosis by intracellular calcium overload via a mitochondrial-mediated pathway. Lactic acid of 20 mM inhibited the apoptosis of MDA-MB-231 cells depending on the glucose insufficiency level, but this inhibition could be eliminated by CUR–Ca(OH)₂-OA/PL NPs, leading to nearly complete apoptosis. Herein, CUR–Ca(OH)₂-OA/PL NPs are a potential killer of cancer cells with high lipase activity by a combination of intracellular calcium overload and lactic acidosis elimination.