pH-Responsive aptamer-linked DNA nanostructures can actively target cancer cells to release drugs in the cells’ acidic environment. Tea polyphenols can be used as cancer-preventive agents to enhance the efficacy of chemotherapeutic drugs. In this study, we constructed a pH-responsive DNA tetrahedron with MUC1 aptamer (MUC1-TD) to co-load irinotecan hydrochloride (CPT-11) and (-)-epicatechin (EC). The thermodynamic parameters for the interaction of CPT-11 and/or EC with MUC1-TD were investigated using fluorescence spectroscopy and calorimetry. The binding of CPT-11 to MUC1-TD was found to be stronger than that of EC. Differential scanning calorimetry and fluorescence quenching experiments demonstrated the intercalative binding between CPT-11/EC and MUC1-TD. The in vitro release rate of CPT-11 was faster at pH 5.0 than at pH 7.4, confirming the pH-responsive of MUC1-TD. In vitro cytotoxicity results indicated that CPT-11 loaded by MUC1-TD was more cytotoxic than free CPT-11. Further, we found that the cytotoxicity of CPT-11 was further enhanced in the presence of EC due to a synergy between them. Additionally, cell uptake experiments showed that CPT-11 and EC loaded by MUC1-TD were mainly distributed in the nucleus of human breast cancer cells (MCF-7). These findings indicate that pH-responsive DNA nanostructures are a promising delivery system for co-loading chemotherapeutic drugs and natural polyphenols.

pH 响应适体连接的 DNA 纳米结构可以主动靶向癌细胞以在细胞的酸性环境中释放药物。茶多酚可作为防癌剂，增强化疗药物的疗效。在这项研究中，我们构建了一个具有 MUC1 适体 (MUC1-TD) 的 pH 响应 DNA 四面体，以共同加载盐酸伊立替康 (CPT-11) 和 (-)-表儿茶素 (EC)。使用荧光光谱和量热法研究了 CPT-11 和/或 EC 与 MUC1-TD 相互作用的热力学参数。发现 CPT-11 与 MUC1-TD 的结合强于 EC。差示扫描量热法和荧光猝灭实验证明了 CPT-11/EC 和 MUC1-TD 之间的嵌入结合。体外_CPT-11 的释放速率在 pH 5.0 时比在 pH 7.4 时更快，证实了 MUC1-TD 的 pH 响应性。体外细胞毒性结果表明，由 MUC1-TD 加载的 CPT-11 比游离 CPT-11 具有更强的细胞毒性。此外，我们发现 CPT-11 的细胞毒性在 EC 存在下由于它们之间的协同作用而进一步增强。此外，细胞摄取实验表明，MUC1-TD 负载的 CPT-11 和 EC 主要分布在人乳腺癌细胞 (MCF-7) 的细胞核中。这些发现表明，pH 响应性 DNA 纳米结构是一种很有前途的递送系统，可用于共同装载化疗药物和天然多酚。