Dendritic Cu²⁺-Doped Ca₂SiO₄ Nanosphere for Cancer Therapy via Double Ion Interference

Abstract

Ion interference therapy (IIT) is a promising cancer treatment strategy that can reverse ion distribution via bioactive nanomaterials so as to interfere with or hinder the physiological processes such as metabolism and proliferation of tumor cells. In this study, a dendritic Cu 2+ -doped calcium silicate nanosphere (Ca 2 SiO 4 ) loaded with ruthenium red (RuR) and disulfiram (DSF) (RD-CCP) was constructed for self-enhanced chemodynamic therapy and IIT of tumors through the combination of Cu and Ca. Under the slightly acidic environment of the tumor, dendritic RD-CCP nanospheres (NPs) rapidly collapsed, and a toxic dithiocarbamate−Cu complex was generated in situ through the chelation reaction between DSF and the co-released Cu 2+ ions. ROS accumulation was promoted by Fenton-like reaction between the Cu + ions and the high level of H 2 O 2 and glutathione. In addition, Ca 2+ -overload was promoted by the combination of the input of exogenous Ca 2+ and the participation of RuR, which can inhibit the Ca 2+ transport channel (MCU and SERCA), therefore promoting mitochondrial damage and enhancing oxidative stress in tumor cells. Furthermore, calcium transport channel imbalance caused by oxidative stress can promote tumor calcification and necrosis. In conclusion, dendritic RD-CCP NPs can simultaneously induce a Fenton-like response and a calcium-related signal imbalance at the tumor site through the double interference of Cu 2+ and Ca 2+ , eventually leading to rapid tumor apoptosis, which has great application potential in the clinical application of tumor therapy.

Mussel-Inspired Tantalum Nanocomposite Hydrogels for In Situ Oral Cancer Treatment

“…In addition, X-ray also causes calcium overload, which is also a factor contributing to irreversible cell damage. 50 By Fluo-4 probe staining, we found that the relative fluorescence intensity of calcium in the Ta@ PVP NPs + X-ray + NIR group was significantly stronger than that of the X-ray group (Figures 4d and S8c). The above experiments indicated that Ta@PVP NPs effectively enhanced X-ray-induced oxidative stress.…”

“…As shown in Figure c,g, the Ta@PVP NPs + X-ray + NIR group had a significant MMP change under the indication of the JC-1 probe and caspase 3 activity enhancement. In addition, X-ray also causes calcium overload, which is also a factor contributing to irreversible cell damage . By Fluo-4 probe staining, we found that the relative fluorescence intensity of calcium in the Ta@PVP NPs + X-ray + NIR group was significantly stronger than that of the X-ray group (Figures d and S8c).…”

Composite Nanoplatforms Based on Nanocalcium Peroxide for Cancer Treatment: From Monotherapy to Combination Therapy

“…As such, understanding intracellular calcium ion homeostasis has become a focal point of antitumor research. [83,84] Disruption of intracellular calcium homeostasis can lead to severe oxidative stress, resulting in cell necrosis, apoptosis, or autophagy-mediated cell death. Therefore, the accumulation of free Ca 2+ in cells represents a critical point of concern, as it can result in calcium overload and the subsequent injury or death of various cell types.…”

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment

“…(3) The released Cu 2+ will be reduced by intracellular glutathione (GSH) to generate Fenton agent Cu + , which can catalyze the self-supplied H 2 O 2 and intrinsic intracellular H 2 O 2 to produce toxic hydroxyl radical by a Cu + -mediated Fenton-like reaction for inducing cell apoptosis. Although previous researches reported the multifunctional nanoplatform with Ca 2+ and Cu 2+ ions, − both of them focused on the generation of toxic hydroxyl radical for inducing cancer cell apoptosis. This study provides innovative ideas for designing Ca 2+ /Cu 2+ dual-ion-based inorganic NPs-induced microenvironmental responsive “ion interference” multimodal nanotherapy platform for inducing paraptosis together with apoptosis and also insight for comprehensive treatment of cancer treatment for better therapeutic effect by apoptosis evasion.…”