Co-delivery of DNAzyme and a chemotherapy drug using a DNA tetrahedron for enhanced anticancer therapy through synergistic effects

A DNA tetrahedron, which could be rapidly and reliably assembled by annealing four customized ssDNA oligonucleotides, has been regarded as one of the most promising nanocarriers. However, engineering of a DNA tetrahedron allowing co-delivery of two or more drugs for synergistic therapy has been largely unexplored. Herein, we report a nanocarrier composed of a DNA tetrahedron (Td), a ZY11-targeting aptamer, anticancer drug doxorubicin (Dox), and 17E DNAzyme to achieve synergistic chemo-gene cancer therapy. First, the nanocarrier was assembled by annealing. Dox can be loaded onto the DNA tetrahedron through intercalation and released in a pH-dependent manner. The obtained Dox@Aptamer-Td-DNAzyme (Dox@Ap-Td-Dz) not only demonstrated an excellent efficiency of gene suppression but also exhibited a good pH-responsive drug release behavior. Hence, the presented DNA tetrahedron based multifunctional nanoplatform can achieve a targeted and synergistic chemo-gene therapy, which provides great potential in improving the curative efficiency.