Advances in Manganese-based nanomaterials for cancer therapy via regulating Non-Ferrous ferroptosis

Ferroptosis, a regulated form of cell death distinct from apoptosis, was first identified in 2012 and is characterized by iron-dependent lipid peroxidation driven by reactive oxygen species (ROS). Since its discovery, ferroptosis has been linked to various diseases, with recent studies highlighting its potential in cancer therapy, particularly for targeting cancer cells that are resistant to traditional treatments like chemotherapy and radiotherapy. While iron has historically been central to ferroptosis, emerging evidence indicates that non-ferrous ions, especially manganese (Mn), also play a crucial role in modulating this process. Mn-based nanomaterials have shown significant promise in cancer treatment by enhancing ROS production, depleting antioxidant defenses, and inducing ferroptosis. Additionally, these materials offer advantages in tumor imaging, immunotherapy, and catalyzing the Fenton-like reactions essential for ferroptosis. This review delves into the mechanisms of Mn-induced ferroptosis, focusing on recent advancements in Mn-based nanomaterials and their applications in chemodynamic therapy and immunotherapy. By leveraging non-ferrous ion-mediated ferroptosis, these approaches provide a novel avenue for cancer treatment. Furthermore, this review explores the potential role of Mn-based nanomaterials in the lipid metabolism pathways involved in ferroptosis and highlights the advantages of Mn ions over other metals in promoting ferroptosis. These insights offer new perspectives for the development of tumor therapies centered on Mn-based nanomaterials.