DNA Nanodevice as a Co-delivery Vehicle of Antisense Oligonucleotide and Silver Ions for Selective Inhibition of Bacteria Growth

DNA nanostructures possess unique programmability and addressability and exhibit a wide variety of potential applications. Recently, they demonstrated their ability to be ideal carriers of antibacterial drugs. In this study, the first use of a DNA six-helix bundle (6HB) nanostructure to co-deliver antisense oligonucleotide (ASO) and silver ions is reported. Although 6HB with Ag⁺ shows excellent antibacterial effect against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, 6HB with ASO selectively inhibits S. aureus. Furthermore, 6HB with both Ag⁺ and ASO exhibits enhanced antibacterial efficacy on S. aureus, probably through two sequential activities. Specifically, Ag⁺-modified 6HB greatly delays bacterial growth by destroying its cell walls, whereas 6HB conjugated with ASO targeting the ftsZ gene of S. aureus effectively inhibits its growth in the logarithmic growth phase by inhibiting the expression of the ftsZ gene. Moreover, this synergistic antibacterial treatment shows excellent biosafety with human normal liver cell L02. This co-delivery system by DNA nanostructures provides a promising platform for antibacterial therapeutics.