Sulfonated vitamin K3 mediated bimetallic metal-organic framework for multistage augmented cancer therapy.
Sulfonated vitamin K3 mediated bimetallic metal-organic framework for multistage augmented cancer therapy.
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DOI：
10.1016/j.jcis.2023.10.016
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发表时间：
2023-10
影响因子：
9.9
通讯作者：
Qiaomei Ke;Peng Jing;Yehong Wan;Tifeng Xia;Ling Zhang;Xianying Cao;Ke Jiang
中科院分区：
文献类型：
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作者：
Qiaomei Ke;Peng Jing;Yehong Wan;Tifeng Xia;Ling Zhang;Xianying Cao;Ke Jiang
基于芬顿反应的化学动力疗法（CDT）已成为一种很有前景的肿瘤治疗策略。然而，其临床疗效受到活性氧（ROS）不足和对正常细胞潜在的细胞毒性的阻碍。为了应对这些挑战，我们已经成功开发了一种基于双金属金属有机框架（BMOF）的多阶段增强癌症治疗系统，该系统可以放大活性氧并促进肿瘤特异性治疗效果。通过简单的一锅自组装方法，我们合成了将磺化维生素K3 （SVK3）包封在ZnCo-ZIF BMOF内的SVK3@ZnCo-ZIF。结果表明，Zn原子的掺入显著稀释了Co原子对正常细胞的芬顿活性。值得注意的是，SVK3@ZnCo-ZIF在肿瘤微环境（tumor microenvironment， TME）触发下进行ph控制分解，从而释放SVK3、Co2+和Zn2+。具体来说，SVK3与NAD(P)H醌氧化还原酶-1 （NQO-1）的相互作用可有效提高肿瘤中的h2o2水平。从而提高了Co2+的芬顿活性。此外，Zn2+离子的释放可诱导细胞功能障碍和线粒体损伤，从而促进ROS的产生和随后的细胞死亡。CDT、SVK3化疗和Zn2+干扰治疗协同联合，极大促进了肿瘤细胞的凋亡。总的来说，我们的研究证明了这种系统在选择性诱导癌细胞毒性的同时最小化对正常细胞的有害影响的有效性。
Chemodynamic therapy (CDT) relying on Fenton reaction has emerged as a promising strategy for tumor treatment. However, its clinical efficacy is hindered by the inadequate reactive oxygen species (ROS) and the potential cytotoxicity towards normal cells. To address these challenges, we have successfully developed a multistage augmented cancer therapy system based on bimetallic metal-organic framework (BMOF) that amplifies ROS and facilitates tumor-specific therapeutic effects. By employing a simple one-pot self-assembly approach, we synthesized SVK3@ZnCo-ZIF in which sulfonated vitamin K3 (SVK3) was encapsulated within ZnCo-ZIF BMOF. The results revealed that the incorporation of Zn atoms significantly diluted the Fenton activity of Co atoms towards normal cells. Notably, SVK3@ZnCo-ZIF underwent pH-controlled decomposition triggered by the tumor microenvironment (TME), thus releasing SVK3, Co2+and Zn2+. Specifically, the H2O2levels in tumors was effectively elevated by the interaction of SVK3 with NAD(P)H quinone oxidoreductase-1 (NQO-1). It thus enhanced the Fenton activity of Co2+. Moreover, the release of Zn2+ions can induce cellular dysfunction and mitochondrial damage, thereby promoting the generation of ROS and subsequent cell death. The synergistic combination of CDT, SVK3 chemotherapy, and Zn2+-interfered therapy greatly facilitated apoptosis of tumor cells. Collectively, our investigations demonstrate the efficacy of such system in selectively inducing toxicity in cancer cells while minimizing detrimental effects on normal cells.