Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, Shaanxi 710119, China.
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China.
ACS Appl Mater Interfaces. 2022 Aug 24;14(33):37280-37290. doi: 10.1021/acsami.2c05944. Epub 2022 Aug 15.
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 (HO) oxidized nanotrains of DNA-CuNCs to produce a lot of Cu 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/HO. Meanwhile, the redox reaction between intracellular glutathione (GSH) and Cu depleted GSH and generated Cu ions, which weakened the antioxidant ability of cancer cells and further enhanced the Fenton-like reaction of Cu/HO, respectively. Thus, the cascade Fenton-like reaction and GSH depletion doubly improved the efficacy of CDT. The and 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.
许多当前的化学动力学治疗（CDT）策略要么治疗效率低，要么缺乏靶向性。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 Fenton 反应效率低下。在此，通过利用功能核酸的多样化功能和可编程性，组装了适体连接的 DNA 铜纳米团簇（aptNTDNA-CuNCs）纳米列车，以在没有外部载体的情况下，将 CDT 试剂靶向识别、装载和递送到肿瘤细胞中。细胞内过氧化氢（HO）将 DNA-CuNCs 的纳米列车氧化，产生大量的 Cu 和 Cu 离子，这些离子可以在弱酸性 TME 中基于与 pH 无关的 Fenton 样反应生成活性氧（ROS）。同时，细胞内谷胱甘肽（GSH）与 Cu 的氧化还原反应耗尽 GSH 并生成 Cu 离子，分别削弱了癌细胞的抗氧化能力，并进一步增强了 Cu/HO 的 Fenton 样反应。因此，级联 Fenton 样反应和 GSH 耗竭双重提高了 CDT 的疗效。体内和体外研究确凿地证实，aptNTDNA-CuNCs 具有优异的抗肿瘤疗效，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、生物相容性和靶向的 CDT。
