Intracellular amplification of oxidative stress has been proved to be an effective strategy to induce cancer cell death and the Fenton reaction was regarded as a robust way to generate ROS which are the main cause of amplified oxidative stress. However, current Fenton reaction-inducing agents lacked stability in the bio-environment and failed to exert their ideal catalytic performance. We, hereby, designed an Fe²⁺-based metal–organic framework (MOF) to deliver Fe²⁺ to cancer cells to trigger the Fenton reaction and produce excessive ROS. The obtained nano-scale MOF that was constructed by ferrous acetate and organic ligands (BDC-NH₂) endowed itself with excellent stability in bio-media and pH responsively degraded itself to release Fe²⁺ in the acid tumor microenvironment. Such a characteristic demonstrated robust capacity to catalyze the Fenton reaction and produce considerable ROS and thus induced distinct Fe²⁺-mediated cell ferroptosis. Meanwhile, directly exploiting an Fe²⁺-based MOF to inhibit and kill cancer cells circumvented the potential adverse effects of loading drugs (like the cardiotoxicity of doxorubicin, and the nephrotoxicity and ototoxicity of cisplatin) and proved to be biocompatible in in vivo experiments. More importantly, observations of the in vivo antitumor experiment attested its impressive inhibition on cancer cells and amelioration on the physical health of treated mice. Our study thus presented a novel and biocompatible ferroptosis strategy to be applied in effective clinical cancer therapy.

中文翻译：

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高度稳定和生物相容性的透明质酸修复的纳米MOF-Fe2 +诱导乳腺癌细胞的肥大病。

氧化应激的细胞内扩增已被证明是诱导癌细胞死亡的有效策略，而Fenton反应被认为是产生ROS的可靠方法，而ROS是放大氧化应激的主要原因。然而，当前的芬顿反应诱导剂在生物环境中缺乏稳定性，并且不能发挥其理想的催化性能。因此，我们设计了一种基于Fe ²⁺的金属有机框架（MOF），以将Fe ²⁺输送至癌细胞以触发Fenton反应并产生过量的ROS。由乙酸亚铁和有机配体（BDC-NH ₂）构建的纳米级MOF在生物介质中具有出色的稳定性，并且pH响应性地降解，从而释放出Fe ²⁺在酸性肿瘤微环境中。这种特征显示出强大的催化Fenton反应并产生大量ROS的能力，从而诱导了明显的Fe ²⁺介导的细胞肥大症。同时，直接利用基于Fe ²⁺的MOF抑制和杀死癌细胞避免了加载药物的潜在不利影响（如阿霉素的心脏毒性以及顺铂的肾毒性和耳毒性），并在体内实验中证明具有生物相容性。更重要的是，体内观察抗肿瘤实验证明了其对癌细胞的令人印象深刻的抑制作用以及对治疗小鼠身体健康的改善。因此，我们的研究提出了一种新颖且具有生物相容性的肥大症治疗策略，可用于有效的临床癌症治疗。