Activatable Dual Cancer-Related RNA Imaging and Combined Gene-Chemotherapy through the Target-Induced IntracellularDisassembly of Functionalized DNA Tetrahedron

The desire for a cancer theranostic system with simultaneouslyaccurate diagnosis and efficient therapy is undeniably interminable. Heretofore,theranostic systems with simple components were designed for cancer theranosticsbut with confined accuracy of diagnosis and side effects of administered drugs. Here,we report an activatable theranostic system for simultaneously imaging dual cancer-related RNAs, mRNA Bcl-2 and piRNA-36026, and combined gene-chemotherapythrough the target-induced intracellular disassembly of DNA tetrahedron. Briefly,fivecustomized oligonucleotides are used to assemble the functionalized DNAtetrahedron. The relevant functional nucleic acids, including the antisequence ofmRNA Bcl-2, the antisequence of piRNA-36026, and aptamer AS1411, are designedin the customized oligonucleotides with the signal reporters Cy3 and Cy5.Doxorubicin (DOX) is loaded in the functionalized DNA tetrahedron by inlayingbetween cytosine and guanine to form the activatable cancer theranostic system. Theactivatable cancer theranostic system is able to recognize MCF-7 cells by aptamer AS1411 and then enter the cells. In the presence oftargets, the antisequences in the activatable cancer theranostic system hybridize with intracellular mRNA Bcl-2 and piRNA-36026,leading to thefluorescence signal recovery of Cy3 and Cy5 and the downregulation of two targets in the cytoplasm as well as theconsequent apoptosis of MCF-7 cells in the form of gene therapy. Interestingly, as the antisequences are designed in the assemblystrands, the hybridization between targets and the antisequences results in the disassembly of the activatable cancer theranosticsystem and the release of DOX as well as sequential chemotherapy. Advantageously, the activatable cancer theranostic system canachieve imaging of dual cancer-related RNAs with an imaging time window as long as 15 h and exhibit an obvious therapeutic effectin vivo. Therefore, this work is in furtherance of exploration for activatable cancer theranostic systems with high accuracy andefficiency and sheds new light on the development of precision medicine.

Automated summary

This study reports an activatable cancer theranostic system that can simultaneously image dual cancer-related RNAs and perform gene therapy. The system shows great potential for accurate diagnosis and efficient treatment of cancer.