In Situ Cation Exchange Generated ZnS-Ag₂S Nanoparticles for Photothermal Detection of Transcription Factor

The photothermal reagent (PTA)-mediated point-of-care detection of disease biomarkers using thermometers as readout has attracted increasing attention, but complex modification or generation process of PTAs still limited their further applications. Herein, we report a photothermal detection platform in which the target recognition triggered the in situ generation of the PTA and ZnS-Ag₂S nanoparticles (NPs) by one-step autonomous cation exchange reaction (ACER). As a proof of concept, NF-kB1, a kind of disease biomarker, was used to demonstrate the photothermal detection platform. First, a triplex-like DNA structure containing the recognition part of NF-kB1 and cytosine-Ag⁺-cytosine (C-Ag⁺-C) unit was designed. With the recognition of NF-kB1, abundant C-Ag⁺-C units were released to take ACER with the prepared ZnS NPs. In addition, because of the intrinsic detecting limitation of the thermometer, hybridization chain reaction (HCR) was introduced to load more Ag⁺ for the enhancement of the photothermal signal. After the irradiation of 808 nm laser toward the generated ZnS-Ag₂S NPs dispersions, its temperature increased with the increased concentration of NF-kB1 in the range from 10 to 1000 nM with a detection limit of 2.31 nM. The signal-amplifying role of HCR was confirmed by the control experiment. This platform of in situ generation of PTA not only integrated the recognition process with detection but also avoided the complex process of modification or generation, which has remarkable potential to be extended for the detections of other different disease biomarkers.