Inducing ferroptosis in breast cancer with nanoparticles: a promising and challenging therapeutic strategy

Breast cancer, marked by its high global incidence and mortality rates, presents significant clinical challenges. Conventional treatments such as surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy often fail to achieve the expected therapeutic efficacy. Ferroptosis, a unique form of regulated cell death driven by iron-dependent lipid peroxidation, has been found to confer higher sensitivity to drug-resistant and highly metastatic breast cancer cells. However, breast cancer therapy based on ferroptosis induction has encountered bottleneck issues such as low stability and poor targeting. Recently, ferroptosis induction via nanoparticles has been explored as a promising strategy and has shown great potential in breast cancer therapy. These nanoparticles, with specific surface modifications, can interfere with iron metabolism, glutathione metabolism, and lipid metabolism through photothermal therapy, photodynamic therapy, or by delivering therapeutic cargo (e.g., drugs, DNA, RNA), ultimately inducing ferroptosis in cancer cells. This review summarizes the characteristics and synthesis methods of nanoparticles designed to induce ferroptosis in breast cancer. We also discuss the mechanisms and clinical potential of different nanoparticle types, as well as future directions in their synthesis, targeting specificity, and biological safety, emphasizing their potential to revolutionize breast cancer treatment.