Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University , Wuhan 430072, P. R. China.
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials; Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, Hubei University , Wuhan, Hubei 430062, P. R. China.
Nano Lett. 2017 Jan 11;17(1):284-291. doi: 10.1021/acs.nanolett.6b04060. Epub 2016 Dec 29.
Discovering advanced materials for regulating cell death is of great importance in the development of anticancer therapy. Herein, by harnessing the recently discovered oxidative stress regulation ability of p53 and the Fenton reaction inducing capability of metal-organic network (MON), MON encapsulated with p53 plasmid (MON-p53) was designed to eradicate cancer cells via ferroptosis/apoptosis hybrid pathway. After confirming the detailed mechanism of MON-p53 in evoking ferroptosis, we further discovered that MON-p53 mediated a "bystander effect" to further sensitize cancer cells toward the MON-p53 induced ferroptosis. A 75-day anticancer experiment indicated that MON-p53 treatment not only suppressed the tumor growth but also prolonged the life-span of tumor bearing mice. Owing to its ability to promote intracellular oxidative stress, MON-p53 decreased the blood metastasis, lung metastasis, and liver metastasis. As a consequence, discovering methods to induce cell ferroptosis would provide a new insight in designing anticancer materials.
发现能够调控细胞死亡的先进材料对于癌症治疗的发展非常重要。在此，我们利用 p53 最近被发现的氧化应激调控能力和金属有机网络（MON）的芬顿反应诱导能力，设计了一种用 MON 封装 p53 质粒（MON-p53）的方法，通过铁死亡/凋亡混合途径来消灭癌细胞。在证实了 MON-p53 诱发铁死亡的详细机制后，我们进一步发现 MON-p53 介导了“旁观者效应”，从而进一步增强了癌细胞对 MON-p53 诱导的铁死亡的敏感性。为期 75 天的抗癌实验表明，MON-p53 治疗不仅抑制了肿瘤生长，还延长了荷瘤小鼠的寿命。由于其促进细胞内氧化应激的能力，MON-p53 减少了血液转移、肺转移和肝转移。因此，发现诱导细胞铁死亡的方法将为设计抗癌材料提供新的思路。
