Oral Presentation 21st International Conference on Biological Inorganic Chemistry 2025

DNA has been employed as a versatile building block for assembling nanomaterials. With predictable Watson-Crick base pairings, low cost, ease of synthesis, and biocompatibility, DNA has become the preferred scaffold to assemble metal nanomaterials for diverse applications. In most cases, DNA and nanomaterial are integrated but both the components retain their independent identity and properties. However, we have identified an unusual DNA structure mediated by metal nanoparticles which in turn influences the property of metal nanomaterial.

One such fluorescent nanomaterial is DNA-stabilized silver nanoclusters (DNA/AgNCs). AgNCs are <2nm in size and exhibit tunable fluorescence, high photostability, and large Stokes shift. Fluorescent AgNCs form metal-mediated base pairing in cytosine-rich DNAs via cytosine-Ag-cytosine base pairing. We have identified a novel mode of interaction among DNA scaffolds mediated by fluorescent AgNCs linking DNA structures.^[1] Moreover, we have identified that dynamic DNA structures can be used to reversibly turn on/off the fluorescent properties of AgNCs.^[1] Our current work with this promising DNA nanomaterial has established principles to rationally design Hoogsteen base-paired triplex DNA secondary structure for synthesizing pH-responsive AgNCs. Through detailed structural investigation, we have defined the arrangement of AgNCs within the Hoogsteen Triplex DNA and how the AgNCs reversibly influence the non-canonical secondary structure of the DNAs. Based on the in-depth understanding of the mutual influence between the host DNA and the associated nanomaterial, AgNCs, on the properties of each other, we have developed a novel biosensor using Tailed-Hoogsteen triplex DNA-encapsulated Silver Nanoclusters (DNA/AgNCs) for microRNA biomarkers detection and imaging.^[2] By altering the biochemical property of DNA, we can rationally tune the stimuli-responsive behavior of AgNCs and/or their fluorescent property. The non-canonical metal nanoclusters-mediated base pairing in DNA holds promise for DNA nanotechnology as nano rivets to be used in conjunction with the Watson–Crick base pairing and for diverse biomedical applications including imaging, sensing, and drug delivery. ^[2]

 References

(1) Nagda R, et.al. ACS Nano, 2022, 16(8), 13211-13222.

(2) H. C. Yadavalli, et.al. Small 2024, 20, 2306793.