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Aptamer-guided DNA tetrahedron as a novel targeted drug delivery system for MUC1-expressing breast cancer cells in vitro

机译:适体指导的DNA四面体作为一种新型靶向药物递送系统用于体外表达MUC1的乳腺癌细胞

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摘要

Mucin 1 (MUC1) is an important molecular target for cancer treatment because it is overexpressed in most adenocarcinomas. In this study, a new MUC1-targeted drug delivery system was assembled using an aptamer (Apt) that could recognize MUC1 and a DNA tetrahedron (Td) that could carry doxorubicin (Dox) within its DNA structure. The complex thus formed (Apt-Td) had an average size of 12.38 nm and was negatively charged. Similar to the MUC1 aptamer, the Apt-Td could preferentially bind with MUC1-positive MCF-7 breast cancer cells. A drug loading experiment revealed that each Apt-Td complex could carry approximately 25 Dox molecules. Moreover, Apt-Td selectively delivered Dox into the MUC1-positive breast cancer cells but reduced Dox uptake by the MUC1-negative control cells. Dox-loaded Apt-Td also induced a significantly higher cytotoxicity to the MUC1-positive cancer cells versus the MUC1-negative control cells in vitro (p<0.01). These results suggest that Apt-Td may potentially serve as a drug carrier in the targeted treatment of MUC1-expressing breast cancers.
机译:粘蛋白1(MUC1)是癌症治疗的重要分子靶标,因为它在大多数腺癌中均过表达。在这项研究中,使用能够识别MUC1的适体(Apt)和可以在其DNA结构内携带阿霉素(Dox)的DNA四面体(Td)组装了新的针对MUC1的药物递送系统。这样形成的络合物(Apt-Td)的平均尺寸为12.38nm,并且带负电。与MUC1适体相似,Apt-Td可优先与MUC1阳性MCF-7乳腺癌细胞结合。载药实验表明,每个Apt-Td复合物可携带约25个Dox分子。此外,Apt-Td选择性地将Dox递送到MUC1阳性乳腺癌细胞中,但减少了MUC1阴性对照细胞对Dox的摄取。载有Dox的Apt-Td与MUC1阴性对照细胞相比,在体外对MUC1阳性癌细胞也具有明显更高的细胞毒性(p <0.01)。这些结果表明,Apt-Td可能在靶向治疗表达MUC1的乳腺癌中充当药物载体。

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