Tumor‐targeted and microenvironment‐activatable iron‐based nMOF for synergistic inducing ferroptosis

• Published in: Applied organometallic chemistry 2024-06, Vol.38 (6), p.n/a
• Main Authors: Gao, Fangxin, Xie, Yaqing, Zhang, Pan, Chang, Qinghua, Zhang, Enli, Shen, Jingyi, Liang, Lili, Zong, Zhihui
• Format: Article
• Language: English
• Subjects: Cell death; drug delivery; Ferroptosis; Folic acid; Glutathione; Iron; Lipids; Loading rate; metal–organic frameworks; nanoparticles; Overloading; Peroxides; Synthesis; Tumors
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.7456

Ferroptosis is a new form of cell death that relies on iron and involves an imbalance of intracellular reactive oxygen species (ROS), which is expected to help alleviate bottlenecks in tumor treatment. Herein, a sorafenib‐loaded folic acid‐armored iron‐based nMOF was designed for synergistic inducing ferroptosis of tumors. The particle size of the synthesized SM@F is about 210nm, and the drug loading rate is 24.74%. SM@F can be degraded and releases sorafenib and iron ions slowly, resulting in intracellular drug release and iron overload after being highly uptaken by SMMC‐7721 cells. SM@F can effectively inhibit the proliferation of SMMC‐7721 cells, and this effect can be significantly attenuated by ferroptosis inhibitors. Mechanistic investigations revealed that SM@F could increase the content of ROS, and lipid peroxides; decrease the content of glutathione (GSH); and down‐regulate the GXP4 expression in SMMC‐7721 cells. The results indicate that the synthesized SM@F could effectively inhibit the proliferation of tumor cells with synergistic inducing ferroptosis. A tumor‐targeting Sorafenib‐loaded FA‐armored iron‐based SM@F with suitable particle size and good biocompatibility was successfully synthesized. The obtained SM@F NPs could target tumor cells, release both Sora and iron in the tumor microenvironment to synergistically induced ferroptosis, effectively inhibit the proliferation, trigger the production of ROS, increase the accumulation of MDA and LPO, and down‐regulate GXP4 expression of SMMC‐7721 cells.