Genomics Research Center, Academia Sinica , Taipei, Taiwan.
Cancer Biol Ther. 2021 Jan 2;22(1):12-18. doi: 10.1080/15384047.2020.1833156. Epub 2020 Nov 29.
We developed a DNA aptamer, Ap52, against the shared tumor-specific MAGE-A3 peptide antigen that was used to target multiple types of cancer cells. Here we report the 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 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.
我们开发了一种针对共享肿瘤特异性 MAGE-A3 肽抗原的 DNA 适体 Ap52，用于靶向多种类型的癌细胞。在这里，我们报告了在植入胰腺肿瘤细胞 AsPC-1 的小鼠中进行的研究，结果表明，无论是静脉内注射还是瘤内注射，修饰后的硫代磷酸酯 Ap52（ThioAp52）都可以在异种移植肿瘤中积累。当与抗肿瘤药物阿霉素（Dox）复合时，ThioAp52 可以靶向递送至包括乳腺癌、口腔癌、胰腺癌和皮肤癌在内的四种类型的癌细胞。图像分析表明，ThioAp52-Dox 复合物选择性进入癌细胞，而游离的 Dox 则被所有细胞系摄取。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，这种针对共享肿瘤特异性抗原的适体可以成为治疗多种癌症的治疗药物的潜在递送载体。
