A nonferrous ferroptosis-like strategy for antioxidant inhibition-synergized nanocatalytic tumor therapeutics.

A nonferrous ferroptosis-like strategy for antioxidant inhibition-synergized nanocatalytic tumor therapeutics.
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抗氧化剂抑制协同纳米催化肿瘤治疗的非铁类铁中毒策略。

DOI:
10.1126/sciadv.abj8833
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发表时间:
2021-09-24
期刊:
影响因子:
13.6
通讯作者:
Shi J
Shi J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wu C;Liu Z;Chen Z;Xu D;Chen L;Lin H;Shi J

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通过使用无机纳米药物进行肿瘤化疗,已经证明了一种非铁性铁中毒样治疗概念。铁凋亡是近几十年来发现的一种新的细胞死亡类型,其特征是细胞死亡过程中的脂质过氧化,通常通过铁的积累。然而,不幸的是,铁物质的直接递送可能引发不期望的有害作用,例如正常组织中的过敏反应。迄今为止,关于使用有色金属元素的细胞铁凋亡的报道很少。在这项工作中,我们提出了一种基于混合CoMoO 4-磷钼酸纳米片(CPMNS)的非铁凋亡样策略,该策略通过加速Mo(V)-Mo(VI)转变,升高GSH消耗以使GPX 4酶失活,以及ROS爆发来实现有效的铁凋亡和化疗。体外和体内结果都证明了显著的抗癌铁凋亡功效,表明这种CPMNS使能的铁凋亡样治疗概念的高度可行性。人们高度期望纳米催化药物中的这种铁凋亡样设计将有益于癌症治疗方案领域的未来进展。
A nonferrous ferroptosis-like therapeutic concept has been demonstrated by using an inorganic nanoagent for tumor chemotherapy. Ferroptosis, an emerging type of cell death found in the past decades, features specifically lipid peroxidation during the cell death process commonly by iron accumulation. Unfortunately, however, the direct delivery of iron species may trigger undesired detrimental effects such as anaphylactic reactions in normal tissues. Up to date, reports on the cellular ferroptosis by using nonferrous metal elements can be rarely found. In this work, we propose a nonferrous ferroptosis-like strategy based on hybrid CoMoO4-phosphomolybdic acid nanosheet (CPMNS)–enabled lipid peroxide (LOOH) accumulation via accelerated Mo(V)-Mo(VI) transition, elevated GSH depletion for GPX4 enzyme deactivation, and ROS burst, for efficient ferroptosis and chemotherapy. Both in vitro and in vivo outcomes demonstrate the notable anticancer ferroptosis efficacy, suggesting the high feasibility of this CPMNS-enabled ferroptosis-like therapeutic concept. It is highly expected that such ferroptosis-like design in nanocatalytic medicine would be beneficial to future advances in the field of cancer-therapeutic regimens.
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