2D Catalytic, Chemodynamic, and Ferroptotic Vermiculite Nanomedicine
2D Catalytic, Chemodynamic, and Ferroptotic Vermiculite Nanomedicine
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DOI：
10.1002/adfm.202208220
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发表时间：
2022-10
影响因子：
19
通讯作者：
Lifang Ma;Hui Huang;Wei Feng;Liang Chen;Lili Xia;Yongchun Yu;Jiayi Wang;Yu Chen
中科院分区：
文献类型：
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作者：
Lifang Ma;Hui Huang;Wei Feng;Liang Chen;Lili Xia;Yongchun Yu;Jiayi Wang;Yu Chen
新兴的化学动力学疗法采用铁基催化芬顿反应将肿瘤微环境（TME）中反应性较低的内源性过氧化氢转化为高毒性的羟基自由基以杀死癌细胞。然而，有效部署的化学动力学模式仍然具有挑战性，陷入了缺乏芬顿剂和过表达的抗氧化剂谷胱甘肽（GSH）在癌细胞。在此，设计了一种基于粘土的2D蛭石纳米片，作为用于有效肺癌治疗的自增强化学动力学纳米剂。工程化的2D蛭石纳米片不仅与正常细胞生物相容，而且能够通过消耗GSH来调节TME，从而改善癌细胞的抗氧化活性。同时，GSH消耗导致细胞内活性氧含量增加和脂质过氧化水平增强，从而诱导铁凋亡和增强化学动力学细胞杀伤效力。特别是，亚铁氧化酶hephaestin是2D蛭石纳米片对抗肺癌细胞的直接治疗靶点。对异种移植肿瘤模型的系统体内评价通过诱导期望的铁凋亡来验证工程化2D蛭石纳米片介导的化学动力学肿瘤疗法的有利的生物安全性和有效的肿瘤抑制能力。因此，开发的蛭石纳米片代表了2D铁凋亡诱导纳米医学的范例，用于协同和有效的癌症治疗。
The emerging chemodynamic therapy employs an iron‐based catalytic Fenton reaction to transform less‐reactive endogenous hydrogen peroxide within the tumor microenvironment (TME) into a highly toxic hydroxyl radical for killing cancer cells. However, the effective deployment of chemodynamic modality remains challenging, mired by a paucity of Fenton agents and overexpressed antioxidant glutathione (GSH) in cancer cells. Herein, a clay‐based 2D vermiculite nanosheet as a self‐reinforcing chemodynamic nanoagent for efficient lung cancer treatment is engineered. The engineered 2D vermiculite nanosheets are not only biocompatible with normal cells but also capable of regulating the TME through depleting GSH, which ameliorates the antioxidant activity of cancer cells. Meanwhile, GSH consumption results in increased intracellular reactive oxygen species content and enhanced lipid peroxidation level, thus inducing ferroptosis and augmenting chemodynamic cell‐killing efficacy. In particular, the ferrous oxidase hephaestin is the direct therapeutic target for 2D vermiculite nanosheets to fight against lung cancer cells. Systematic in vivo evaluations on a xenografted tumor model verify the favorable biosafety and effective tumor suppression capacity of the engineered 2D vermiculite nanosheets‐mediated chemodynamic tumor therapy by inducing desirable ferroptosis. Therefore, the developed vermiculite nanosheets represent the paradigm of 2D ferroptosis‐inducing nanomedicine for synergistic and efficient cancer treatment.