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Self-Cycling Free Radical Generator from LDH-Based Nanohybrids for Ferroptosis-Enhanced Chemodynamic Therapy
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2021-07-28 , DOI: 10.1002/adhm.202100539
Xueting Yang 1, 2 , Li Wang 2, 3 , Shuaitian Guo 1, 2 , Ran Li 1, 2 , Fangzhen Tian 2, 3 , Shanyue Guan 2 , Shuyun Zhou 2 , Jun Lu 1, 4
Affiliation  

Nonapoptotic ferroptosis has been a novel form of programmed cell death, which provides a new solution to enrich the anticancer treatment efficacy of traditional apoptotic therapeutic modality. Herein, a novel nanohybrid is designed by loading the PEG-encapsulated Artemisinin (denoted as A@P) on the ultrathin MgFe-LDH nanosheets (denoted as uLDHs) for improved chemodynamic therapy (CDT). The A@P/uLDHs cannot only realize the self-assembly between the Art and carrier but also be regarded as free radical generator. A comprehensive mechanistic study suggests that this unique A@P/uLDHs is able to in situ activate Art and self-cycling generate toxic C-centered free radical inside the cancer cells, without depending on abundant H2O2, accompanied with diminished cancerous antioxidation by depleting glutathione (GSH). The accumulation of ROS and depletion of GSH can further oxidize unsaturated fatty acid to generate lipid peroxide, whose overexpression can induce cell ferroptosis accompanied by cellular iron homeostasis turbulence. Both in vitro and in vivo results exhibit that A@P/uLDHs are an efficient nanoagent for highly efficient ferroptosis-enhanced CDT treatment. This work imparts the promising new visions about the ferroptosis-enhanced CDT via fine regulation of material design for improved cancer treatments.

中文翻译:

来自基于 LDH 的纳米杂化物的自循环自由基发生器,用于铁死亡增强的化学动力学治疗

非凋亡性铁死亡是一种新的程序性细胞死亡形式,为丰富传统凋亡治疗方式的抗癌治疗效果提供了新的解决方案。在此,通过在超薄 MgFe-LDH 纳米片(表示为 uLDHs)上加载 PEG 包封的青蒿素(表示为 A@P)设计了一种新型纳米杂化物,用于改进化学动力学治疗(CDT)。A@P/uLDHs不仅可以实现Art和载体之间的自组装,还可以看作是自由基发生器。一项全面的机理研究表明,这种独特的 A@P/uLDHs 能够原位激活 Art 并自循环在癌细胞内产生有毒的以 C 为中心的自由基,而不依赖于丰富的 H 2 O 2,伴随着通过消耗谷胱甘肽(GSH)而降低的癌性抗氧化作用。ROS的积累和GSH的消耗可以进一步氧化不饱和脂肪酸产生脂质过氧化物,其过表达可以诱导细胞铁死亡并伴随细胞铁稳态紊乱。体外和体内结果均表明,A@P/uLDHs 是一种高效的纳米试剂,可用于高效的铁死亡增强 CDT 治疗。这项工作通过精细调节材料设计以改善癌症治疗,为铁死亡增强 CDT 带来了有希望的新愿景。
更新日期:2021-09-22
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