Cationic-Polyelectrolyte-Modified Fluorescent DNA–Silver Nanoclusters with Enhanced Emission and Higher Stability for Rapid Bioimaging

DNA-templated silver nanoclusters (DNA–Ag NCs) have shown great potential in various bioanalysis and bioimaging applications, owing to their facile synthesis and ultrasmall sizes and especially their programmable fluorescence emission depending on the sequences of DNA templates. However, the bioimaging applications of DNA–Ag NCs are severely limited by their poor stability in physiological environments and their poor cell permeability, resulting from the highly negatively charged DNA backbones. In this paper, cationic polyelectrolytes were used to modify fluorescent DNA–Ag NCs via electrostatic interactions between the positive polymer backbones and the negatively charged phosphate groups of the DNA strands. The fluorescence properties of a typical single-stranded-DNA (ssDNA)-templated Ag NC changed dramatically after incorporation with the cationic polyelectrolyte caused by conformational changes in the DNA, with a 3-fold fluorescence-emission enhancement of the Ag NCs observed after incorporation with a typical cationic polyelectrolyte, poly­(diallyldimethylammonium chloride) (PDDA), whereas the fluorescence of double-stranded-DNA (dsDNA)-templated Ag NCs changed little after incorporation. Moreover, the modification with PDDA greatly prolonged the stability of both ssDNA- and dsDNA-stabilized Ag NCs against nuclease digestion and enhanced the cell uptake of the DNA–Ag NCs. Rapid cell imaging was demonstrated using NIH/3T3 cells as a model system.