Copper ions amplify the oxidative stress caused by calcium overload leading to apoptosis

作者：Shiwei Liu, Wennan Yan, Ji Zhang, Ziyi Li, Yingshu Guo · 发表于：Biomedical Analysis · 年份：2024 · DOI：10.1016/j.bioana.2024.05.001 · 被引用次数：3 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoparticles: synthesis and applications、Sulfur Compounds in Biology

Reactive Oxygen Species (ROS) therapy based on metal ion catalysis had attracted much attention due to its high selectivity for tumour cells and lower side effects. Copper ions (Cu2+) show great potential in tumour therapy due to their efficient fenton-like catalysis. However, the accumulation and utilisation efficiency of copper ions within the cell was limited, hence the need for efficient delivery of Cu2+ into the cell. Curcumin (CUR) not only acted as a ligand to bind copper ions, but also acted as an electron donor to increase the fenton-like catalytic efficiency of Cu+ and enhance the generation of ROS. Calcium carbonate (CaCO3) nanoparticles had good biocompatibility, alleviated the microacidic environment of tumours and released calcium ions (Ca2+) to trigger calcium overload leading to apoptosis. Therefore, in the present study, CaCO3 nanoparticles (CRC@lip) loaded with curcumin and Cu2+ were designed and modified with liposomal surface to improve their stability and dispersion in vivo. CRC@lip generated Cu+ with higher catalytic activity by releasing Cu2+, and reacting with glutathione (GSH). Cu+ catalyzed the generation of highly toxic ·OH radicals by H2O2, while the electron donor property of CUR further enhanced the stability and dispersal of the nanoparticles. The electron-donor property of CUR further enhanced the catalytic effect and amplified the killing effect on tumour cells through the interaction of calcium overload and ROS. This strategy not only improve...