A novel targeted co-delivery system for transfer of epirubicin and antimiR-10b into cancer cells through a linear DNA nanostructure consisting of FOXM1 and AS1411 aptamers

Herein, a novel linear DNA nanostructure (LDN)-based delivery system was designed and prepared to efficiently co-deliver both epirubicin (Epi), as a chemotherapy drug, and antimiR-10b, as a therapeutic oligonucleotide, into breast cancer cells (MCF-7 and 4T1 cells). Firstly, the LDN, comprised of AS1411 aptamer (targeting agent), FOXM1 Apt (therapeutic aptamer), and complementary strand (linker), was prepared to carry both Epi and antimiR-10b. This targeted system is highly stable in serum and easy to be constructed. The Epi-loaded LDN structure showed a remarkable internalization for target cells (MCF-7 and 4T1 cells, nucleolin positive) in comparison with CHO cells (nucleolin negative, non-target). Furthermore, based on the MTT assay, the Epi-loaded LDN significantly decreased the cell viability of MCF-7 and 4T1 cells, while the non-targeted cells indicated less cytotoxicity for this structure, showing the targeting ability of Epi-loaded LDN. Moreover, the ability of tumor growth inhibition of the Epi-loaded LDN structure was significantly much more than free Epi and LDN in tumor-bearing mice, suggesting the significance of combination therapy for tumor treatment.