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首页> 外文期刊>RSC Advances >A novel aptamer-based DNA diamond nanostructure for in vivo targeted delivery of epirubicin to cancer cells
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A novel aptamer-based DNA diamond nanostructure for in vivo targeted delivery of epirubicin to cancer cells

机译：一种新型的基于适体的DNA金刚石纳米结构，用于体内靶向表柔比星向癌细胞的递送

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The clinical administration of epirubicin (Epi) in the treatment of cancer has been restricted, owing to its cardiotoxicity. Targeted delivery of anticancer agents could increase their therapeutic efficacy and decrease their off-target effects. In this study, a novel Epi-DNA diamond nanostructure (DDN) conjugate containing two kinds of aptamers (MUC1 and ATP aptamers) was designed and evaluated in the treatment of target cells, including C26 cells (murine colon carcinoma cell) and MCF-7 cells (breast cancer cell). DDN and Epi-DDN conjugate formations were analyzed by gel retardation assay and fluorometric analysis, respectively. Release profiles of Epi from the developed Epi-DDN conjugate were evaluated at pHs 5.4 and 7.4. For the MTT assay (cell viability study), CHO cells (Chinese hamster ovary cell, nontarget), C26 and MCF-7 cells (target) were treated with the Epi-DDN conjugate, DDN, Epi, Epi-DDN conjugate without ATP aptamer and Epi-DDN conjugate without MUC1 aptamer. Internalization of the Epi-DDN conjugate was assessed by flow cytometry analysis and fluorescence imaging. Finally, the designed Epi-DDN conjugate was utilized for inhibition of tumor growth in vivo. 10 μM Epi was efficiently loaded in 1 μM DDN. The drug was released from the Epi-DDN conjugate in a pH-sensitive manner (higher release in acidic conditions). The results of flow cytometry analysis and fluorescence imaging confirmed that the developed Epi-DDN conjugate was effectively internalized into target cells, but not into nontarget cells. The results of the MTT assay were consistent with the internalization data. The Epi-DDN conjugate had more cytotoxicity in MCF-7 and C26 cells and less cytotoxicity in CHO cells in comparison with Epi alone. Moreover, the Epi-DDN conjugate could effectively prohibit tumor growth in vivo.
机译：由于其心脏毒性，表柔比星（Epi）的临床治疗受到了限制。靶向递送抗癌药可以提高其治疗效果并降低脱靶作用。在这项研究中，设计并评估了包含两种适体（MUC1和ATP适体）的新型Epi-DNA金刚石纳米结构（DDN）共轭物，并评估了其对靶细胞的治疗效果，包括C26细胞（鼠结肠癌细胞）和MCF-7细胞（乳腺癌细胞）。 DDN和Epi-DDN共轭物的形成分别通过凝胶阻滞分析和荧光分析进行了分析。在pH 5.4和7.4下评估了Epi从已开发的Epi-DDN共轭物的释放曲线。为了进行MTT分析（细胞活力研究），将CHO细胞（中国仓鼠卵巢细胞，非靶标），C26和MCF-7细胞（靶标）用Epi-DDN缀合物，DDN，Epi，Epi-DDN缀合物（不含ATP适体）处理和不含MUC1适体的Epi-DDN共轭物。 Epi-DDN共轭物的内部化通过流式细胞仪分析和荧光成像进行评估。最后，将设计的Epi-DDN缀合物用于体内抑制肿瘤生长。将10μMEpi有效地加载到1μMDDN中。药物以pH敏感的方式从Epi-DDN偶联物中释放出来（在酸性条件下释放更高）。流式细胞仪分析和荧光成像的结果证实，开发的Epi-DDN共轭物可以有效地内化到靶细胞中，而不是非靶细胞中。 MTT测定的结果与内在化数据一致。与单独的Epi相比，Epi-DDN共轭物在MCF-7和C26细胞中具有更高的细胞毒性，而在CHO细胞中具有更低的细胞毒性。此外，Epi-DDN偶联物可以有效地抑制肿瘤在体内的生长。

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