School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Nanoscale Horiz. 2021 Apr 1;6(4):348-356. doi: 10.1039/d0nh00674b. Epub 2021 Mar 9.
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 HO 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.
非凋亡性细胞死亡，如铁死亡和细胞焦亡，为癌症治疗带来了新的曙光，而这两种机制的联合治疗尚未得到充分探索。在此，提出了一种用于实现铁死亡/细胞焦亡介导的抗癌作用的双重诱导纳米系统。该纳米药物（Tf-LipoMof@PL）由载有胡椒碱（PL）的金属有机骨架（MOF）组成，该 MOF 涂覆有转铁蛋白修饰的 pH 敏感脂质层。含有铁的 MOF 可使细胞内铁富集，而脂质层上的转铁蛋白修饰可进一步促进其内化，这为铁死亡和细胞焦亡的发生提供了前提条件。胡椒碱作为铁死亡诱导剂，可增强铁死亡细胞死亡，并通过芬顿反应为双重诱导系统提供 HO 以增加 ROS 生成。在验证了铁死亡和细胞焦亡之后，双重诱导的纳米药物在异种移植小鼠模型中显示出理想的抗癌效果，这证明了铁死亡/细胞焦亡双重诱导纳米平台可能是一种有效且有前途的抗癌方式。
