Gold nanoparticles conjugated DNA-tile nanomaterials for simultaneous delivery of morpholino antisense oligonucleotides and doxorubicin

Current therapies have limited treatment effect on cancer. Combinational delivery of multiple therapeutics has been commonly investigated to enhance the therapeutic outcome of the disease. The carrier systems have the great importance for effective co-delivery of the multiple drugs. In this report, we demonstrated a DNA nanomaterial for simultaneous delivery of morpholino antisense oligonucleotides (AONs) and doxorubicin to breast cancer cells. DNA-tile nanostructures were prepared by embedding morpholino oligos against ERα and HER2 genes and the morpholino embedded DNA-tiles were modified with gold nanoparticles by sticky-ended association to obtain increased internalization. Then the DNA-carrier was loaded with doxorubicin. Morpholino and doxorubicin therapeutics were successfully delivered to breast cancer cells. It was observed that the co-delivery system showed 50% enhanced intracellular uptake of the chemotherapy drug, better cytotoxic effect and significantly higher level of cell cycle arrest than free doxorubicin at targeted receptor-positive breast cancer cells. The obtained results indicated that the proposed nanosystem is an effective delivery vehicle for combinational cancer therapies and increased anti-cancer activity of chemotherapy.