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大蒜素修饰的 FeOOH 纳米催化药物用于促进铁/铁循环的高效和持续肿瘤消退。

Allicin‒Decorated FeOOH Nanocatalytic Medicine for Fe/Fe Cycling‒Promoted Efficient and Sustained Tumor Regression.

机构信息

Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200072, P. R. China.

School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, P. R. China.

出版信息

Adv Sci (Weinh). 2024 Aug;11(32):e2402801. doi: 10.1002/advs.202402801. Epub 2024 Jun 20.

Abstract

In the tumor treatment by Fenton reaction‒based nanocatalytic medicines, the gradual consumption of Fe(II) ions greatly reduces the production of hydroxyl radicals, one of the most active reactive oxygen species (ROS), leading to much deteriorated therapeutic efficacy. Meanwhile, the ROS consumption caused by the highly expressed reduced glutathione (GSH) in the tumor microenvironment further prevents tumor apoptosis. Therefore, using the highly expressed GSH in tumor tissue to promote the Fe(III) reduction to Fe(II) can not only weaken the resistance of tumor to ROS attack, but also generate enough Fe(II) to accelerate the Fenton reaction. In view of this, an allicin‒modified FeOOH nanocatalyst possessing varied valence states (II, III) has been designed and synthesized. The coexistence of Fe(II)/Fe(III) enables the simultaneous occurrence of Fenton reaction and GSH oxidation, and the Fe(III) reduction by GSH oxidation results in the promoted cyclic conversion of Fe ions in tumor and positive catalytic therapeutic effects. Moreover, allicin capable of regulating cell cycle and suppressing tumor growth is loaded on FeOOH nanosheets to activate immune response against tumors and inhibit tumor recurrence, finally achieving the tumor regression efficiently and sustainably. This therapeutic strategy provides an innovative approach to formulate efficient antitumor nanomedicine for enhanced tumor treatment.

摘要

在基于芬顿反应的纳米催化药物治疗肿瘤中,Fe(II)离子的逐渐消耗会大大降低羟基自由基(ROS)这一最活跃的活性氧物种之一的产生,从而导致治疗效果大大恶化。同时,肿瘤微环境中高表达的还原型谷胱甘肽(GSH)引起的 ROS 消耗进一步阻止了肿瘤细胞凋亡。因此,利用肿瘤组织中高表达的 GSH 促进 Fe(III)还原为 Fe(II),不仅可以削弱肿瘤对 ROS 攻击的抵抗力,还可以生成足够的 Fe(II)来加速芬顿反应。有鉴于此,设计并合成了一种具有变价态(II、III)的大蒜素修饰的 FeOOH 纳米催化剂。Fe(II)/Fe(III) 的共存使芬顿反应和 GSH 氧化同时发生,GSH 氧化还原的 Fe(III)导致肿瘤内 Fe 离子的促进循环转化和积极的催化治疗效果。此外,负载在 FeOOH 纳米片上的能够调节细胞周期和抑制肿瘤生长的大蒜素可以激活针对肿瘤的免疫反应并抑制肿瘤复发,最终高效、持续地实现肿瘤消退。这种治疗策略为制定高效抗肿瘤纳米药物提供了一种创新方法,以增强肿瘤治疗效果。

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