One-Pot Rapid Synthesis of Cu2+-Doped GOD@MOF to Amplify the Antitumor Efficacy of Chemodynamic Therapy,ACS Applied Materials & Interfaces

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One-Pot Rapid Synthesis of Cu2+-Doped GOD@MOF to Amplify the Antitumor Efficacy of Chemodynamic Therapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-03-27 , DOI: 10.1021/acsami.3c00562
Qing Li ₁ , Jiantao Yu ₁ , Li Lin ₁ , Yulin Zhu ₂ , Zixiang Wei ₁ , Feiyan Wan ₁ , Xindan Zhang ₁ , Feng He ₂ , Leilei Tian ₁

Affiliation

Chemodynamic therapy (CDT) relies on the transformation of intracellular hydrogen peroxide (H₂O₂) to hydroxyl radicals (·OH) with higher toxicity under the catalysis of Fenton/Fenton-like reagents, which amplifies the oxidative stress and induces significant cellular apoptosis. However, the CDT efficacy is generally limited by the overexpressed GSH and insufficient endogenous H₂O₂ in tumors. Co-delivery of Cu²⁺ and glucose oxidase (GOD) can lead to a Cu²⁺/Cu⁺ circulation to realize GSH depletion and amplify the Fenton-like reaction. pH-responsive metal–organic frameworks (MOFs) are the optical choice to deliver Fenton/Fenton-like ions to tumors. However, considering that the aqueous condition is requisite for GOD encapsulation, it is challenging to abundantly dope Cu²⁺ in ZIF-8 MOF nanoparticles in aqueous conditions due to the ease of precipitation and enlarged crystal size. In this work, a robust one-pot biomimetic mineralization method using excessive ligand precursors in aqueous conditions is developed to synthesize GOD@Cu-ZIF-8. Copper ions abundantly doped to the GOD@Cu-ZIF-8 can eliminate GSH to produce Cu⁺, which is further proceeded to the Fenton-like reaction in the presence of GOD-catalyzed H₂O₂. Through breaking the tumor microenvironment homeostasis and producing an enhanced CDT effect, the promising antitumor capability of GOD@Cu-ZIF-8 was evidenced by the experiments both in vitro and in vivo.

中文翻译：

一锅法快速合成 Cu2+ 掺杂的 GOD@MOF 以增强化学动力学疗法的抗肿瘤功效

化学动力学疗法（CDT）依赖于细胞内过氧化氢（H ₂ O ₂）在Fenton/Fenton-like试剂的催化下转化为毒性更高的羟基自由基（·OH），从而放大氧化应激并诱导显着的细胞凋亡. 然而，CDT 的功效通常受到肿瘤中过度表达的 GSH 和不足的内源性 H ₂ O _{2的限制。}^{Cu 2+}和葡萄糖氧化酶 (GOD)的共同递送可导致 Cu ²⁺ /Cu ⁺循环以实现 GSH 消耗并放大 Fenton 样反应。pH 响应性金属有机框架 (MOF) 是将芬顿/类芬顿离子递送至肿瘤的光学选择。然而，考虑到水性条件是 GOD 封装所必需的，由于易于沉淀和晶体尺寸增大，因此在水性条件下大量掺杂 Cu ²⁺到 ZIF-8 MOF 纳米颗粒中具有挑战性。在这项工作中，开发了一种在水性条件下使用过量配体前体的稳健的一锅仿生矿化方法来合成 GOD@Cu-ZIF-8。大量掺杂到GOD@Cu-ZIF-8中的铜离子可以消除GSH产生Cu ^{+ ，在GOD催化的H}₂ O存在下进一步进行类芬顿反应₂ . 通过打破肿瘤微环境稳态并产生增强的 CDT 效应，体外和体内实验证明了 GOD@Cu-ZIF-8 具有良好的抗肿瘤能力。

更新日期：2023-03-27

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