Yan Yuyan, Han Renlu, Zhang Huijun, Song Pengxin, Wei Xiangjun, Hou Yafei, Yu Jiancheng, Tang Keqi
Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis, Institute of Mass Spectrometry, School of Materials Science & Chemical Engineering, Ningbo University, Ningbo 315211, PR China.
Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis, Institute of Mass Spectrometry, School of Materials Science & Chemical Engineering, Ningbo University, Ningbo 315211, PR China.
Colloids Surf B Biointerfaces. 2023 Jan;221:112997. doi: 10.1016/j.colsurfb.2022.112997. Epub 2022 Oct 31.
Chemodynamic therapy (CDT), which employs Fenton/Fenton-like agents to decompose hydrogen peroxide (HO) into toxic hydroxyl radical (•OH) to induce cancer cell apoptosis and necrosis, holds great promise in tumor therapy due to its high selectivity. Nevertheless, its efficiency is impaired by the insufficient intracellular HO concentration and/or the insensitive response of Fenton/Fenton-like agents to the slightly acid tumor microenvironment (pH∼7.0-6.5). Herein, we develop a novel CDT reagent based on CeO quantum dot (QD) decorated MgO nanosheets engineered with cascade reactions to boost the intracellular HO level and high pH-activated (pH = 6.5) characteristic for an enhanced CDT. Under the tumor microenvironment (pH = 6.5), MgO nanosheets that are highly reactive can react with HO to produce nontoxic Mg and abundant HO, boosting the intracellular HO level. The self-generated HO is subsequently converted into •OH by CeO QD, which is served as a relatively high pH-activated (pH = 6.5) Fenton-like agent. The sufficient intracellular HO supply and sensitive response to the slightly acid tumor sites significantly improve the Fenton reaction, leading to the excellent in vivo CDT results with tumor growth inhibition effect. Our work presents a distinctive paradigm for self-boosting CDT efficacy.
化学动力疗法（CDT）利用芬顿/类芬顿试剂将过氧化氢（H₂O₂）分解为有毒的羟基自由基（•OH）以诱导癌细胞凋亡和坏死，因其高选择性在肿瘤治疗中具有广阔前景。然而，细胞内H₂O₂浓度不足和/或芬顿/类芬顿试剂对微酸性肿瘤微环境（pH∼7.0 - 6.5）的不敏感响应会削弱其疗效。在此，我们基于CeO量子点（QD）修饰的MgO纳米片开发了一种新型CDT试剂，通过级联反应设计以提高细胞内H₂O₂水平，并具有高pH激活（pH = 6.5）特性以增强化学动力疗法。在肿瘤微环境（pH = 6.5）下，高反应性的MgO纳米片可与H₂O₂反应生成无毒的Mg和大量H₂O₂，提高细胞内H₂O₂水平。随后，自生的H₂O₂被CeO量子点转化为•OH，CeO量子点作为一种相对高pH激活（pH = 6.5）的类芬顿试剂。细胞内充足的H₂O₂供应以及对微酸性肿瘤部位的敏感响应显著改善了芬顿反应，从而在体内产生了具有肿瘤生长抑制效果的优异化学动力疗法结果。我们的工作为自我增强化学动力疗法疗效提供了一种独特的范例。
