A pH-sensitive DNA tetrahedron for targeted release of anthracyclines: Binding properties investigation and cytotoxicity evaluation

The anticancer efficacy of chemotherapeutic agents can be enhanced by the loading of DNA nanostructures, which is closely related to their interactions. This study achieved pH-responsive and targeted anthracycline delivery using i-motif and MUC1 aptamer co-modified DNA tetrahedron (MUC1-TD). The thermodynamic pa-rameters for the binding of doxorubicin (DOX) and epirubicin (EPI) to MUC1-TD at pHs 7.4 and 5.0 were ob-tained. The smaller binding constant and the number of binding sites at pH 5.0 than at pH 7.4 indicated that acidic conditions favored the release of DOX and EPI loaded by MUC1-TD. The binding affinity of DOX was stronger than that of EPI at the same pH value due to their different chemical stereostructures. The intercalative binding mechanism was verified. In vitro release experiments revealed that acid pH and deoxyribonuclease I accelerated the release of DOX and EPI. The faster release rate of EPI than DOX was related to their binding affinity. In vitro cytotoxicity and cell uptake experiments revealed that the cytotoxicity of DOX and EPI loaded by MUC1-TD to MCF-7 cells was significantly higher than that to L02 cells. This work will provide theoretical guidance for the application of pH-responsive MUC1-TD nanocarriers in the field of pharmaceutics.