The Polymer Society of Korea

Immunogenic cell death (ICD) is a promising strategy to enhance anti-tumor immunity, yet clinically viable ferroptosis-mediated ICD approaches remain limited. Here, we develop self-assembled polysaccharide–doxorubicin nanoparticles coordinated with Fe³⁺ ions (~200 nm). After tumor accumulation, pH-responsive disassembly releases doxorubicin and iron ions to trigger lipid peroxidation and ferroptotic cell death. In vitro, these nanoconstructs induced ROS generation, GPX4 suppression, and ICD hallmarks such as calreticulin (CRT) exposure and HMGB1 release. Ex vivo profiling revealed enhanced dendritic cell activation and increased CD4⁺ T cell infiltration. In vivo, treatment suppressed tumor growth and prolonged survival with minimal toxicity, while co-treatment with the GPX4 inhibitor ML210 synergistically improved therapeutic efficacy. Overall, this polysaccharide-based nanoplatform integrates chemotherapy and ferroptosis for ICD-driven cancer immunotherapy.