Multifunctional Double-Bundle DNA Tetrahedron for Efficient Regulation of Gene Expression

DNA nanostructures have garnered considerable interest as research tools in the field of cell biology and pathology. Herein, we develop an addressable double-bundle DNA tetrahedron with distinct modification sites to load multiple functional components for efficient regulation of gene expression. In our tailored nanoplatform, nucleic acid drugs (antisense for gene therapy) and protein drugs (KillerRed for photodynamic therapy) are precisely organized in the chemically well-defined DNA tetrahedron. With the attachment of active targeting groups, this functional DNA nanocarrier can efficiently penetrate into the cell membrane and subsequently transport drugs to the target subcellular organelles (mitochondrion and nucleus) for inducing synergistic cell behavior regulation to start the endogenous apoptotic process. This tailored DNA nanocarrier provides unprecedented opportunities for intelligent drug delivery and cell biology research.