Non-apoptotic cell death such as ferroptosis and pyroptosis has shed new light on cancer treatment, whereas combinational therapy using both these mechanisms has not yet been fully explored. Herein, a dual-inductive nano-system to realize ferroptosis/pyroptosis mediated anti-cancer effects is presented. The nanodrug (Tf-LipoMof@PL) is constructed with a piperlongumine (PL) loaded metal–organic framework (MOF) coated with transferrin decorated pH sensitive lipid layer. Intracellular iron was enriched with an iron-containing MOF, whose endocytosis can be further facilitated by transferrin decorated on the lipid layer, which provides a prerequisite for the occurrence of ferroptosis and pyroptosis. Piperlongumine as the ferroptosis inducer can strengthen the ferroptotic cell death, and provide H₂O₂ for the dual induction system to increase ROS generation through Fenton reaction. On the basis of validation of both ferroptosis and pyroptosis, the dual-inductive nanodrug demonstrated ideal anticancer effects in the xenograft mice model, which proved that the ferroptosis/pyroptosis dual-inductive nanoplatform could be an effective and promising anticancer modality.

中文翻译：

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转铁蛋白修饰的纳米MOF实现铁死亡/细胞焦亡双诱导联合抗癌治疗

非凋亡细胞死亡如铁死亡和细胞焦亡为癌症治疗提供了新的思路，而使用这两种机制的联合治疗尚未得到充分探索。在此，提出了一种实现铁死亡/细胞焦亡介导的抗癌作用的双诱导纳米系统。纳米药物 (Tf-LipoMof@PL) 由负载胡椒胺 (PL) 的金属有机骨架 (MOF) 构成，并涂有转铁蛋白修饰的 pH 敏感脂质层。细胞内铁富含含铁的 MOF，脂质层上装饰的转铁蛋白可以进一步促进其内吞作用，这为铁死亡和细胞焦亡的发生提供了先决条件。胡椒龙胺作为铁死亡诱导剂可以加强铁死亡细胞死亡，并提供H ₂ O ₂双诱导系统通过芬顿反应增加 ROS 的产生。在对铁死亡和细胞焦亡的验证的基础上，双诱导纳米药物在异种移植小鼠模型中表现出理想的抗癌作用，证明铁死亡/细胞焦亡双诱导纳米平台可能是一种有效且有前景的抗癌方式。