Surface-Controlled Modulation of Copper Nanocluster–DNA Interaction and Its Implication for Targeted Biological Applications

The present study aims to investigate the role of surface ligands in governing the binding interaction between copper nanoclusters (CuNCs) and deoxyribonucleic acid (DNA) in order to assess their potential for biotherapeutic applications. For this purpose, CuNCs having three chemically different surface ligands, namely, tannic acid (TA), chitosan (Cht), and cysteine (Cys), are synthesized and characterized using various analytical methods. The binding interaction studies were performed at both ensemble average and single-molecule levels by exploiting several spectroscopic and microscopic techniques. Initial investigations have revealed that cysteine-capped copper nanoclusters (Cys-CuNCs) follow a one-step binding mechanism, whereas tannic acid-capped copper nanoclusters (TA-CuNCs) and chitosan-capped copper nanoclusters (Cht-CuNCs) exhibit a two-step binding process while interacting with DNA. Additionally, circular dichroism measurements have provided valuable information about the structural integrity of DNA when exposed to different CuNCs. Furthermore, fluorescence correlation spectroscopic measurement has depicted that the binding interaction events between CuNCs and DNA are different for the three different CuNCs, even at the single-molecule level. Notably, the outcome of the present investigations has suggested that the accumulation of DNA bases in the presence of Cht-CuNCs, along with their weak intermolecular interactions with DNA, can make Cht-CuNCs highly suitable for gene therapy. Conversely, TA-CuNCs and Cys-CuNCs may hold significant potential for bioimaging and biosensing applications due to their ability to maintain DNA’s structural integrity and their good biocompatibility. Overall, this study has effectively highlighted the crucial role of surface ligands in nanoscale materials for modulating DNA interactions and emphasized their potential in targeted biological applications.