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.