铁转运蛋白
海西定
癌症研究
髓系白血病
免疫疗法
白血病
癌症
癌细胞
药理学
免疫系统
生物
医学
免疫学
炎症
内科学
作者
Lingxiao Zhang,Yue Song,Kunxia Cao,Yangyang Du,Mingda Han,Zhan Shi,Fei Yan,Shouhua Feng
标识
DOI:10.1002/adfm.202107195
摘要
Abstract Despite recent advances in targeted therapies and immunotherapies in acute myeloid leukemia, patient prognosis is still dismal given the high frequency of refractory cases or post‐remission relapse. Ferrotherapy, a novel anti‐cancer treatment strategy using iron‐based compounds, can mechanistically bypass the chemoresistance of cancer cells. However, cancer cells often overexpress the transmembrane iron exporter ferroportin that expels accumulated iron into the plasma, which can potentially limit the efficacy of ferrotherapy and lead to systemic toxic effects. Here, a ferro‐therapeutic nanoplatform is designed using fusing hepcidin and leukemia cell‐membrane vesicles on gold nanoparticles (AuNPs)‐loaded hollow mesoporous Prussian Blue (AuPB@LMHep). AuPB@LMHep specifically targeted leukemia cells through ferroportin and is subsequently internalized and disintegrated into iron and AuNPs through autophagy. The accumulation of iron due to blockade of ferroportin‐mediated iron efflux and the depletion of glutathione by the AuNPs triggered ferroptosis. Furthermore, iron accumulation inactivated the endogenous iron‐dependent m 6 A demethylase, thereby increasing global m 6 A RNA modification and suppressing multiple oncogenes. Finally, AuPB@LMHep enhanced the immune response to anti‐programmed death ligand1 treatment via increasing cytotoxic tumor‐infiltrating T cells. Pre‐clinical findings provide the proof‐of‐concept of hepcidin‐based nanocomposite as an “epigenetic drug” and immunotherapeutic agent for treating leukemia.
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