“Ferroptosis-immune” cycle: Research progress of tumor microenvironment responsive nanomaterials in the treatment of pancreatic cancer

Pancreatic cancer (PC) therapy is hindered by a dense stroma and immunosuppressive microenvironment. Ferroptosis, an iron-dependent cell death, has emerged as a promising therapeutic strategy. This review introduces the "ferroptosis-immune" cycle concept. Ferroptosis in tumor cells not only directly kills them but also releases damage-associated molecular patterns that promote antitumor immunity. Conversely, activated immune cells enhance ferroptosis sensitivity in tumor cells. Precisely initiating this cycle remains a key challenge. We focus on tumor microenvironment-responsive nanomaterials as innovative tools that enable controlled co-delivery of ferroptosis inducers and immune modulators, thereby amplifying the synergistic ferroptosis-immune cycle. Current challenges and future directions are discussed, providing a theoretical foundation for developing novel nanotherapies for PC based on ferroptosis-immunity synergy.