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, making tumor-specific induction of PANoptosis a potential cancer therapeutic strategy. Currently, cancer treatment research related to PANoptosis is mainly focused on the development of small molecules and cytokines. However, these approaches still face limitations in terms of metabolic stability and tumor specificity. The development of nanotechnology offers new opportunities for cancer treatment by improving targeting efficiency, extending circulation time, and enhancing therapeutic efficacy and safety. Additionally, the unique physicochemical properties of nanomaterials can effectively optimize PANoptosis induction strategies, establishing nanomaterials as ideal candidates for inducing PANoptosis in tumor cells. 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. This review will inspire further exploration and development of PANoptosis-based cancer treatments, providing new perspectives for researchers in the field.