触发级联类芬顿反应和谷胱甘肽消耗的 DNA 铜纳米团簇纳米链可双重增强化学动力学治疗,ACS Applied Materials & Interfaces

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触发级联类芬顿反应和谷胱甘肽消耗的 DNA 铜纳米团簇纳米链可双重增强化学动力学治疗
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-08-15 , DOI: 10.1021/acsami.2c05944
Qianqian Li ₁ , Fei Wang ₂ , Lu Shi ₁ , Qiaorong Tang ₁ , Baoxin Li ₁ , Xiaobing Wang ₂ , Yan Jin ₁

Affiliation

许多当前的化学动力学治疗（CDT）策略要么治疗效率低，要么靶向性差。治疗效率低主要归因于细胞内抗氧化系统和弱酸性肿瘤微环境（TME）中低效的芬顿反应。在此，通过利用功能性核酸的多种功能和可编程性，组装了适配子连接的 DNA 铜纳米簇 (aptNTDNA-CuNCs) 纳米链，以同时实现 CDT 试剂的靶向识别、加载和递送到肿瘤细胞中，而无需外部载体. 细胞内过氧化氢 (H ₂ O ₂ ) 氧化 DNA-CuNCs 的纳米链产生大量的 Cu ²⁺和 Cu ⁺^{基于Cu +} /H ₂ O ₂的不依赖pH的类芬顿反应，可在弱酸性TME中产生活性氧（ROS）。同时，细胞内谷胱甘肽（GSH）与Cu ²⁺发生氧化还原反应，消耗GSH，生成Cu ⁺离子，削弱癌细胞的抗氧化能力，进一步增强Cu ⁺ /H ₂ O ₂的类芬顿反应。因此，级联 Fenton 样反应和 GSH 消耗双倍提高了 CDT 的功效。体内和体外_研究证实aptNTDNA-CuNCs具有优异的抗肿瘤功效，对健康细胞无细胞毒性。因此，aptNTDNA-CuNCs 可以作为 CDT 试剂实现高效、生物相容性和靶向性 CDT。

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Nanotrains of DNA Copper Nanoclusters That Triggered a Cascade Fenton-Like Reaction and Glutathione Depletion to Doubly Enhance Chemodynamic Therapy

Many current chemodynamic therapy (CDT) strategies suffer from either low therapeutic efficiency or the deficiency of poor targeting. The low therapeutic efficiency is mainly ascribed to the intracellular antioxidant system and the inefficient Fenton reaction in the weakly acidic tumor microenvironment (TME). Herein, by exploitation of the diverse function and programmability of functional nucleic acid, aptamer-tethered nanotrains of DNA copper nanoclusters (aptNTDNA-CuNCs) were assembled to simultaneously achieve targeted recognition, loading, and delivery of CDT reagents into tumor cells without an external carrier. The intracellular hydrogen peroxide (H₂O₂) oxidized nanotrains of DNA-CuNCs to produce a lot of Cu²⁺ and Cu⁺ ions, which can generate reactive oxygen species (ROS) in the weakly acidic TME based on the pH-independent Fenton-like reaction of Cu⁺/H₂O₂. Meanwhile, the redox reaction between intracellular glutathione (GSH) and Cu²⁺ depleted GSH and generated Cu⁺ ions, which weakened the antioxidant ability of cancer cells and further enhanced the Fenton-like reaction of Cu⁺/H₂O₂, respectively. Thus, the cascade Fenton-like reaction and GSH depletion doubly improved the efficacy of CDT. The in vivo and in vitro study solidly confirmed that aptNTDNA-CuNCs have excellent antitumor efficacy and no cytotoxicity to healthy cells. Therefore, aptNTDNA-CuNCs can act as CDT reagents to achieve highly efficient, biocompatible, and targeted CDT.

更新日期：2022-08-15

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