脱甲基酶
髓系白血病
谷胱甘肽
白血病
化学
癌症研究
干细胞
细胞生物学
生物
生物化学
免疫学
表观遗传学
酶
基因
作者
Kunxia Cao,Yangyang Du,Xiaoyi Bao,Mingda Han,Rui Su,Jiuxia Pang,Shujun Liu,Zhan Shi,Fei Yan,Shouhua Feng
出处
期刊:Small
[Wiley]
日期:2022-02-04
卷期号:18 (13)
被引量:42
标识
DOI:10.1002/smll.202106558
摘要
The N6-methyladenosine (m6 A) demethylase FTO plays an oncogenic role in acute myeloid leukemia (AML). Despite the promising recent progress for developing some small-molecule FTO inhibitors, the clinical potential remains limited due to mild biological function, toxic side effects and low sensitivity and/or specificity to leukemic stem cells (LSCs). Herein, FTO inhibitor-loaded GSH-bioimprinted nanocomposites (GNPIPP12MA) are developed that achieves targeting of the FTO/m6 A pathway synergized GSH depletion for enhancing anti-leukemogenesis. GNPIPP12MA can selectively target leukemia blasts, especially LSCs, and induce ferroptosis by disrupting intracellular redox status. In addition, GNPIPP12MA increases global m6 A RNA modification and decreases the transcript levels in LSCs. GNPIPP12MA augments the efficacy of the PD-L1 blockade by increasing the infiltration of cytotoxic T cells for enhanced anti-leukemia immunity. This study offers insights for a GSH-bioimprinted nanoplatform targeting m6 A RNA methylation as a synergistic treatment strategy against cancer stem cells that may translate to clinical applications.
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