Cascade Catalytic Nanozymes Induce Tumor Ca²⁺ Overload and Ferroptosis by Reducing Energy Supply and Amplifying Oxidative Stress

》》文章原文链接：Cascade Catalytic Nanozymes Induce Tumor Ca²⁺ Overload and Ferroptosis by Reducing Energy Supply and Amplifying Oxidative Stress

》》Journal：ACS Applied Materials & Interfaces

》》相关产品：HPF (SJ-MD0109)

》》产品引用描述：

》》Abstract：

Nanozyme-mediated nanocatalytic therapy, by mimicking the activity of redox enzymes, generates highly toxic reactive oxygen species (ROS) within tumor cells, thereby opening a pathway for tumor-specific therapy. However, achieving satisfactory therapeutic outcomes with nanozymes remains challenging due to the inherent complexity of the tumor microenvironment (TME). In this context, we designed a two-dimensional layered double hydroxide (LDH) nanozyme loaded with Au nanoparticles, while incorporating bioactive Ca²⁺ and Fe³⁺ ions (denoted as MgCaFe-LDH@Au NSs) to target the specific needs of the TME. The designed nanozyme mimics glucose oxidase to facilitate self-sufficient H₂O₂ production and simulates catalase and glutathione peroxidase to overcome the adverse conditions of hypoxia and elevated GSH levels in the TME. Subsequently, the nanozyme emulates peroxidase activity to generate ROS, amplifying oxidative stress and causing redox imbalance, ultimately inducing ferroptosis in tumor cells. Moreover, MgCaFe-LDH@Au NSs also function as an inorganic semiconductor sonosensitizer with a tunable band structure, enabling the generation of abundant ROS under ultrasound irradiation to achieve synergistic sonodynamic and catalytic therapy. Notably, the high levels of ROS induced by the nanozyme, along with the interference in tumor ATP synthesis, enhanced the calcium overload in the TME caused by the release of Ca²⁺ from the nanozyme. In summary, this two-dimensional nanomaterial, through nanozyme and ultrasound-catalyzed synergistic disruption of tumor energy supply and redox balance, exhibited significant therapeutic efficacy in a 4T1 tumor-bearing mouse model. This study also highlights the immense potential of multimetal LDHs as inducers of calcium overload and ferroptosis in tumor therapy.