ABSTRACT

We developed a DNA aptamer, Ap52, against the shared tumor-specific MAGE-A3_111-125 peptide antigen that was used to target multiple types of cancer cells. Here we report the in vivo study of mice implanted with pancreatic tumor cells AsPC-1, which demonstrates accumulation of phosphorothioate-modified Ap52 (ThioAp52) at the xenograft tumor following either intravenous or in situ injection. When complexed with antitumor drug doxorubicin (Dox), ThioAp52 achieves targeted delivery to four types of cancer cells, including breast, oral, pancreatic, and skin. Image analysis shows that ThioAp52-Dox complex selectively enters cancer cells, while free Dox is taken up by all cell lines. The cytotoxicity of ThioAp52-Dox for cancer cells is enhanced as compared to that for the corresponding normal/noncancerous cells. These results indicate that this aptamer against shared tumor-specific antigen can be a potential delivery vehicle for therapeutics to treat multiple cancers.

摘要

我们针对共享的肿瘤特异性 MAGE-A3 _111-125肽抗原开发了一种 DNA 适体 Ap52，该抗原用于靶向多种类型的癌细胞。在这里，我们报告了植入胰腺肿瘤细胞 AsPC-1 的小鼠的体内研究，该研究表明，在静脉内或原位注射后，硫代磷酸酯修饰的 Ap52 (ThioAp52) 在异种移植肿瘤中积累注射。当与抗肿瘤药物阿霉素 (Dox) 复合时，ThioAp52 可靶向递送至四种类型的癌细胞，包括乳腺癌、口腔癌、胰腺癌和皮肤癌。图像分析显示，ThioAp52-Dox 复合物选择性地进入癌细胞，而游离的 Dox 被所有细胞系吸收。与相应的正常/非癌细胞相比，ThioAp52-Dox 对癌细胞的细胞毒性增强。这些结果表明，这种针对共有肿瘤特异性抗原的适体可以成为治疗多种癌症的潜在载体。