Amifostine–Iron Nanoparacrystalline for Tumor-Selective Immunogenic Ferroptosis

作者：Zhusheng Huang, Hao Zhou, Shiqian Huang, Shaoyin Zhang, Simin Song, Yalin Zhang, Yunlu Dai, Lixing Weng, Lianhui Wang, Zhimin Luo · 发表于：Nano Letters · 年份：2025 · DOI：10.1021/acs.nanolett.5c05065 · 被引用次数：1 · 研究领域：Ferroptosis and cancer prognosis、Nanoplatforms for cancer theranostics、Cancer, Hypoxia, and Metabolism

Ferroptosis offers potent anticancer potential but suffers from nonselective toxicity and immune suppression. Here, we develop amifostine–iron nanoparacrystalline (AFe-NPC), a self-delivering nanomedicine assembled from a clinically approved cytoprotective prodrug and ferric ions, enabling tumor-selective immunogenic ferroptosis. AFe-NPC with good T 2 -weighted magnetic resonance imaging (MRI) contrast exhibits superior Fenton catalytic activity and potent glutathione depletion, outperforming commercial Fe 3 O 4 nanoparticles for enabling efficient ferroptosis induction under MRI guidance. Notably, alkaline phosphatase (ALP) with high expression in normal cells can convert amifostine in AFe-NPC into WR-1065, which scavenges reactive oxygen species and upregulates Col3a1 and Col12a1 to enhance ALP activity for strengthening cytoprotection. Conversely, low ALP expression in tumor cells cannot realize effective cytoprotection, causing AFe-NPC to induce immunogenic ferroptosis. AFe-NPC-induced ferroptosis can boost CD8 + T cell-mediated systemic anticancer immunity and synergize with immune checkpoint blockade to eradicate primary and metastatic tumors.