NIR light-mediated tumor ferroptosis therapy: a new perspective for multi-modal synergistic therapy

Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a promising strategy for cancer treatment because of its distinct mechanism and potential to overcome conventional drug resistance. However, its clinical application remains limited by insufficient tumor targeting, pronounced heterogeneity of the tumor microenvironment, and limited adaptability to individualized treatment. Near-infrared (NIR) imaging provides deep tissue penetration and a low autofluorescence background, offering a feasible approach to spatiotemporally controlled ferroptosis induction and real-time therapeutic monitoring. This review systematically summarizes recent advances in NIR imaging-guided ferroptosis-based therapies and organizes current strategies according to a hierarchical progression from single-modality therapy to dual- and multimodal combinations. We discuss the distinct synergistic mechanisms and design principles at each level and identify major barriers to clinical translation. This framework may provide practical guidance for selecting appropriate combination modalities, designing multifunctional platforms with compatible mechanisms, and developing individualized therapeutic strategies. Finally, we highlight current challenges and future directions for the clinical translation of ferroptosis-targeted theranostics.