Nanomaterials-Induced PANoptosis: A Promising Anti-Tumor Strategy.

Malignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become a critical strategy for cancer treatment. PANoptosis, a newly discovered form of regulated cell death, integrates key molecular components of pyroptosis, apoptosis, and necroptosis, activating these three death pathways simultaneously to achieve synergistic multi-mechanistic killing. PANoptosis significantly inhibits cancer cell growth and resistance and activates strong anti-tumor immune response, making tumor-specific induction of PANoptosis a potential cancer therapeutic strategy. Currently, cancer treatment research related to PANoptosis is focused mainly on the development of small molecules and cytokines. However, these approaches still face limitations in terms of metabolic stability and tumor specificity. The unique physicochemical properties and biological activities of nanomaterials hold significant promise for optimizing PANoptosis induction strategies. This review summarizes the concept and mechanisms of PANoptosis, highlights the latest applications of nanoagents in PANoptosis-based anti-cancer therapy, and discusses the challenges and future directions for clinical translation. It is hoped that this review will inspire further exploration and development of PANoptosis-based cancer treatments, providing new perspectives for researchers in the field.