The Polymer Society of Korea

류수현 (서울대학교)

이강원 (서울대학교)

Ferroptosis is a promising anticancer modality but can paradoxically induce immune resistance via PD-L1 upregulation. We present a checkpoint-silenced immuno-ferroptotic nanoplatform that integrates ferroptosis induction with PD-L1 gene silencing. Hyaluronate-coated iron oxide nanoparticles carrying PD-L1 siRNA (IONP-PDL1siR@HA) preferentially accumulate in CD44-overexpressing tumors, enabling coordinated iron delivery and RNA interference. Upon cellular uptake, the platform enhances iron-driven ROS generation, lipid peroxidation, and GPX4 depletion to induce ferroptosis while concurrently suppressing PD-L1 expression. In a syngeneic breast tumor model, IONP-PDL1siR@HA achieves superior tumor suppression compared with ferroptosis alone, accompanied by increased CD8⁺ T-cell infiltration. These findings demonstrate a nanomaterial strategy to overcome ferroptosis-associated immune escape and enhance antitumor efficacy.