Photothermal Ferrotherapy - Induced Immunogenic Cell Death via Iron-Based Ternary Chalcogenide Nanoparticles Against Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS2, is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC. AgFeS2 possesses excellent photothermal conversion performance for tumor near-infrared (NIR) phototherapy. Upon photoirradiation, these NPs generate heat, accelerate the release of iron ions, and effectively catalyze the Fenton reaction, resulting in cell apoptosis and ferroptosis. Additionally, AgFeS2 promotes the release of tumor-specific antigens and triggers an immune response via immunogenic cell death (ICD), thereby providing unique synergistic mechanisms for cancer therapy. The present study demonstrates the great potential of iron-based ternary chalcogenide as a new therapeutic platform for a combination of photothermal therapy, ferrotherapy, and immunotherapy for the suppression of TNBC. An iron-based ternary chalcogenide nanoparticle exhibits excellent photothermal conversion performance and effective ability of ROS generation under NIR laser irradiation. The results of in vitro and in vivo studies show that this nanoparticle not only directly kills the tumor cells through apoptosis and ferroptosis pathways but also triggers robust immune response via immunogenic cell death in the treatment of TNBC.image