This study demonstrated a
chemotherapy drug-free delivery system for
breast cancer treatment based on a simple
DNA nanostructure composed of sequence 1 containing
ATP and
AS1411 aptamers and sequence 2 containing antimiR-21. The
DNA nanostructure was used for co-delivery of
KLA peptide and antimiR-21 as antiapoptotic agents. These therapeutic agents could not be internalised into eukaryotic cells freely which is one of the great features of this targeting platform. The presented delivery system was
ATP-responsive, leading to disassembly of the
DNA nanostructure in high
ATP concentration of
cancer cells and restoration of the function of antimiR-21 in these cells. The
DNA nanostructure was associated with high cellular uptake by MCF-7 and 4T1 cells due to expression of
nucleolin as target of
AS1411 on their plasma membranes, while the developed targeting platform could not be internalised into CHO cells because of lack of the active targeting moiety on their surfaces. Furthermore, the results showed that co-delivery of antimiR-21 and
KLA peptide using the
DNA nanostructure could efficiently prohibit tumour growth in vitro and in vivo and induce a synergistic anticancer activity. Thus, this work provides a new
ATP-responsive nanotargeting delivery system and synergistic
chemotherapy drug-free regimen for
cancer treatment.