A versatile NiS2/FeS2 hybrid nanocrystal for synergistic cancer therapy by inducing ferroptosis and pyroptosis

作者：Xu, Shuxiang; Zhou, Shuyi; Xie, Luoyijun; Dou, Wenlong; Zhang, Rongjun; Zhao, Bingxia; Xu, Yang^*; Fu, Xuemei^*; Yuan, Miaomiao^*

来源：Chemical Engineering Journal, 2023, 460: 141639.

DOI：10.1016/j.cej.2023.141639

• Epithelial-Mesenchymal Transition (EMT)
• Ferroptosis
• Pyroptpsis
• Synergistic cancer therapy
• Tumor immunity

Due to the heterogeneous and complex tumor microenvironment (TME), it remains challenging to effectively treat solid tumors with monotherapy. The development of a versatile nanomaterial strategy for synergistic chemodynamic/photodynamic/photothermal therapies has the potential to overcome this challenge. Herein, we designed and synthesized NiS2/FeS2 hybrid nanoparticles (NiS2/FeS2 NPs), which are further modified with polyvinyl pyrrolidone (PVP) to improve their biocompatibility. PVP-NiS2/FeS2 NPs exhibit synergistic activities of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) with multi-modal imaging capabilities. With the presence of Fe2+/Fe3+ and Ni2+/Ni3+ redox couples, the PVP-NiS2/FeS2 NPs exhibit GSH peroxidase-like reactivity and trigger Fenton reaction, leading to robust .OH generation and pyroptosis/ferroptosis after near infared irradiation (NIR). In response to the PVP-NiS2/FeS2 NPs and PVP-NiS2/ FeS2 NPs + NIR treatment, the breast tumors formed in the syngeneic BABL/c mice were eliminated and their metastases suppressed by inhibiting the EMT pathway. Consistent with the apparent involvement of these pro-grammed cell death pathways in activating tumor immunity, we demonstrate that PVP-NiS2/FeS2 NPs + NIR can eliminate metastatic tumors in an immune system dependent manner. Therefore, PVP-NiS2/FeS2 NPs represent a promising strategy to treat metastatic breast cancer.

• 单位
  上海交通大学; 中山大学; 浙江大学; y; 南方医科大学