A Ferroptosis-Inducing Arsenene-Iridium Nanoplatform for Synergistic Immunotherapy in Pancreatic Cancer

Due to multidrug resistance and the high risk of recurrence, effective and less toxic alternative pancreatic cancer treatments are urgently needed. Pancreatic cancer cells are highly resistant to apoptosis but sensitive to ferroptosis. In this study, an innovative nanoplatform (AsIr@PDA) was developed by electrostatic adsorption of a cationic iridium complex (IrFN) onto two-dimensional (2D) arsenene nanosheets. This nanoplatform exhibits superior ferroptosis-inducing effects with high drug loading capacity and, importantly, excellent anti-cancer immune activation function, leading to efficient elimination of pancreatic tumors with no observable side effects. Interestingly, AsIr@PDA significantly prevents the recurrence of pancreatic cancer in vivo when compared with a cisplatin-loaded nanoplatform. This designed nanoplatform demonstrated superior therapeutic efficacy by synergistic ferroptosis-induced chemotherapy with immunotherapy via an all-in-one strategy, providing new insights for future pancreatic cancer therapy. We designed an innovative arsenene-iridium nanoplatform AsIr@PDA by loading ferroptosis-inducing metal complex IrFN on arsenene nanosheets. The effective release of IrFN from AsIr@PDA induced pancreatic cancer cell ferroptosis, and the ferroptotic cell death together with the immunomodulatory arsenene endows AsIr@PDA with a superior therapeutic effect by synergistic ferroptosis-induced chemotherapy and immunotherapy via an all-in-one strategy.+ image