CuS-NiS2 nanomaterials for MRI guided phototherapy of gastric carcinoma via triggering mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS-NiS2 nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer in vitro and in vivo without obvious side effects. We revealed that CuS-NiS2 induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS-NiS2 and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS-NiS2 exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS-NiS2, which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.