Multivalent aptamer-modified tetrahedral DNA nanocage demonstrates high selectivity and safety for anti-tumor therapy

Abstract

The fabrication of aptamers on DNA nanostructures through the DNA origami method has shown great potential for in vitro and in vivo tumor targeting delivery. Herein, tetrahedral multivalent DNA (Td) nanocages modified with different numbers of MUC1-aptamers (nApt-Td) were obtained via the self-assembly of nucleic acid backbones containing the aptamer DNA fragment without complicated chemical modification steps. Then, doxorubicin (DOX) was encapsulated in the modified nApt-Td nanocages via non-covalent interactions. Due to the specific identification of the aptamers, the intracellular uptake studies demonstrated that the multivalent modified aptamers on the vertex of Td significantly enhanced the intracellular uptake efficiency in MCF-7 tumor cells, but reduce that of normal cells. The number of aptamers had a significant influence on the intracellular uptake efficiency of Td nApt-Td. Furthermore, improved in vivo systemic safety and decreased systemic toxicity accompanied with effective tumor inhibition were also demonstrated compared with the anti-tumor efficiency of free DOX.