Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, 117576 Singapore, Singapore.
J Pharm Sci. 2012 May;101(5):1672-7. doi: 10.1002/jps.23101. Epub 2012 Mar 1.
A single-stranded DNA aptamer (APT) capable of targeting mucin 1 (MUC1) extracellular protein was modified to increase its drug delivery specificity toward MUC1 overexpressing cancer cell line, MCF7. The active targeting region of APT was truncated and variable repeats (one, two, or three) of this sequence were synthesized. An aptamer formed from three repeats of this active targeting region (L3) was shown to possess enhanced doxorubicin (DOX) intercalation ability, and L3-DOX complex exhibited selective cytotoxicity to MCF7 over RAW cells. Most importantly, L3 was able to evade RAW 264.7 macrophages (2-fold reduction in L3 uptake relative to APT), thus resulting in an overall 5.5-fold increase of survivability of RAW cells as compared with when free DOX was used. These results indicate that aptamer L3 has good potential for targeted drug therapeutics.
一种能够靶向黏蛋白 1（MUC1）细胞外蛋白的单链 DNA 适体（APT）经过修饰，以提高其对过度表达 MUC1 的癌细胞系 MCF7 的药物输送特异性。APT 的主动靶向区域被截断，并合成了该序列的一个、两个或三个可变重复序列。由该主动靶向区域的三个重复序列形成的适体（L3）显示出增强的阿霉素（DOX）插入能力，并且 L3-DOX 复合物对 MCF7 细胞具有选择性细胞毒性，而对 RAW 细胞没有毒性。最重要的是，L3 能够逃避 RAW 264.7 巨噬细胞（相对于 APT，L3 的摄取减少了 2 倍），因此与使用游离 DOX 相比，RAW 细胞的存活率提高了 5.5 倍。这些结果表明，适体 L3 具有用于靶向药物治疗的良好潜力。
