AML‐Targeted Metal‐Polyphenol Nanoplatform Induces Ferroptosis‐ICD Cascade for Antitumor Immunity Boosting

作者：Shangqin Yang, Jingxuan Wang, Kerong Tu, Xiaobing Huang, Lin Lv, Mingjie Peng, Qiqi Xu, Hailong Liu, Qiang Sun, lulu Cai · 发表于：Advanced Science · 年份：2026 · DOI：10.1002/advs.202520544 · 被引用次数：2 · 研究领域：Ferroptosis and cancer prognosis、Immune cells in cancer、Phagocytosis and Immune Regulation

ABSTRACT Acute myeloid leukemia (AML) remains a therapeutic challenge due to its low immunogenicity and immunosuppressive tumor microenvironment (iTME). We developed a ferritin‐based nanoplatform (Fe‐SH@Fn) co‐delivering shikonin (SH) and Fe 3+ to synergistically induce ferroptosis and activate immunogenic cell death (ICD). Ferritin, a ligand for CD71, which is overexpressed on AML cells, enables tumor targeting and encapsulates Fe‐SH formed by coordination between SH and Fe 3+ . In AML cells, high intracellular glutathione triggers Fe‐SH@Fn disassembly: Fe 3+ reduces to Fe 2+ to drive Fenton reaction‐mediated ferroptosis, while SH induces ICD. This dual effect boosts the release of damage‐associated molecular patterns, remodeling the microenvironment by promoting dendritic cell maturation, enhancing CD8 + T cell infiltration, and reducing regulatory T cells. In vivo, Fe‐SH@Fn achieved 81.25% tumor growth inhibition in subcutaneous AML model and extended median survival by 2.8‐fold in orthotopic AML model without systemic toxicity. This work presents a translatable strategy that overcomes AML immunosuppression through targeted drug delivery and synergistic ferroptosis‐ICD activation.