Suppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer, which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Owing to its poor water solubility and limited intracellular iron content, it is challenging for further application in antitumor therapy. Herein, we developed ferrous-supply nano-carrier for ART based on tannic acid (TA) and ferrous ion (Fe(II)) coated on the zeolitic imidazolate framework-8 (ZIF) with ART encapsulated (TA-Fe/ART@ZIF) via coordination-driven self-assembly. Drug release experiments showed that ART was not nearly released in pH 7.4, while 59% ART was released in pH 5.0 after 10 h, demonstrating the excellent pH-triggered release. Meanwhile, a high level of intracellular ROS and MDA, accompanied with decreasing GSH and GPX4, displayed a newly developed nano-drug system displayed markedly enhanced ferroptosis. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated higher efficiency of tumor suppression of TA-Fe/ART@ZIF. This work provides a novel approach to enhance the potency of ferroptotic nano-medicine and new directions for TBNC therapy.

通过诱导肥大症抑制肿瘤的发展可能为三阴性乳腺癌提供一种潜在的治疗方法，这种乳腺癌对细胞内的氧化失衡很敏感。近来，青蒿素（ART）及其衍生物已被研究为潜在的抗癌药，可通过铁介导的内过氧化物桥的裂解诱导肥大症来治疗高度侵袭性癌症。由于其水溶性差和细胞内铁含量有限，因此在抗肿瘤治疗中进一步应用具有挑战性。在本文中，我们开发了基于鞣酸（TA）和亚铁离子（Fe（II））的ART的亚铁供体纳米载体，该载体涂覆在ART封装的（TA-Fe / ART @ ZIF）沸石咪唑酸酯骨架8（ZIF）上）通过协调驱动的自组装。药物释放实验表明，在pH 7.4下ART几乎没有释放，而在10 h后在pH 5.0上释放了59％的ART，这证明了pH触发的优异释放。同时，高水平的细胞内ROS和MDA，伴随着GSH和GPX4的降低，显示出新开发的纳米药物系统，其显着增强了肥大症。与单一疗法相比，体外和体内肿瘤抑制实验表明，TA-Fe / ART @ ZIF抑制肿瘤的效率更高。这项工作提供了一种新颖的方法，以增强铁磁纳米药物的效力，并为TBNC治疗提供了新的方向。展示了新开发的纳米药物系统，该系统显着增强了肥大症。与单一疗法相比，体外和体内肿瘤抑制实验表明，TA-Fe / ART @ ZIF抑制肿瘤的效率更高。这项工作提供了一种新颖的方法，以增强铁磁纳米药物的效力，并为TBNC治疗提供了新的方向。展示了新开发的纳米药物系统，该系统显着增强了肥大症。与单一疗法相比，体外和体内肿瘤抑制实验表明，TA-Fe / ART @ ZIF抑制肿瘤的效率更高。这项工作提供了一种新颖的方法，以增强铁磁纳米药物的效力，并为TBNC治疗提供了新的方向。