A Co-catalytic nanosystem based on molybdenum disulfide and Prussian blue for synergistic chemodynamic and photothermal therapy through mitochondrial damage and ferroptosis

Abstract

Chemodynamic therapy (CDT) is regarded as an emerging strategy with high specificity for tumor therapy by producing highly toxic reactive oxygen species (ROS) in tumor cells by a Fenton or Fenton-like reaction. Excessive ROS can cause mitochondrial damage and induce ferroptosis in cells, leading to the death of cancer cells. However, the generally low efficiency of the Fenton reaction has limited the effectiveness of CDT. Herein, two-dimensional MoS₂ decorated with PB NPs is used as a co-catalyst to promote Fe^III/Fe^II conversion and thus enhance the efficiency of the Fenton reaction. The photothermal properties of both MoS₂ and PB NPs further enhance the Fenton reaction, eventually producing a large amount of ROS. Mitochondrial damage and ferroptosis caused by ROS are evidenced in vitro and in a tumor-bearing mouse model and jointly lead to a decrease in heat shock protein content, further enhancing the photothermal effect of PB NP/MoS₂ nanosystem. This chemodynamic/photothermal synergistic therapy allows achieving good anticancer therapeutic effect.

Statement of significance

CDT is a promising cancer treatment that selectively generates toxic ROS to eliminate tumor cells. Nevertheless, its efficacy is often limited by the low efficiency of the Fenton reaction. This study presents a nanocomposite composed of MoS₂ nanosheets decorated with PB NPs, which enhances CDT by improving Fe^III/Fe^II conversion and increasing ROS production. In addition, the photothermal properties of the material further amplify its therapeutic effects. In cell and animal models, this synergistic approach effectively induces mitochondrial damage and ferroptosis, thereby weakening the defenses of the cancer cells. This work provides a significant advancement in CDT, offering a more potent strategy for cancer therapy.