Work

Nanoenhanced‐Cuproptosis Results From the Synergy of Calcium Overload and GSH Depletion with the Increasing of Intracellular Ca/Mn/Cu Ions

Year: 2025

Type: article

Abstract: Cuproptosis is a newly discovered copper‐dependent form of cell death. Intracellular glutathione (GSH) acts as a copper chelator to inhibit cuproptosis, so the reduction of GSH concentration is conducive to enhancing the cuproptosis of cells. In order to reduce GSH content and interfere with mitochondrial metabolism, a strategy based on calcium overload and GSH depletion to enhance cuproptosis is proposed in this study. Containing manganese (Mn) and copper (Cu) elements, CaCO3 nanoparticles (NPs) are modified with MCF‐7 cell aptamer (CaCO3/Mn/Cu@lip‐Apt). When entering the cell, CaCO3/Mn/Cu@lip‐Apt decomposed and released Mn* (Mn2+/Mn3+/Mn4+), Cu2+ and Ca2+. The high valence Mn ion in Mn* can effectively consume GSH to produce Mn2+ which catalyzed H2O2 to produce reactive oxygen species (ROS), while reducing the GSH concentration. The production of ROS promoted the influx of exogenous Ca2+. The large accumulation of Ca2+ led to intracellular calcium overload, resulting in mitochondrial dysfunction and metabolism disorders. The depletion of GSH promoted the accumulation of Cu2+, which in turn triggered cuproptosis. This strategy showed excellent antitumor effects and provided a new way to study disease treatment.

Source: Advanced Science

DOI: 10.1002/advs.202412067