Multifunctional Gold Nanoclusters-Based Nanosurface Energy Transfer Probe for Real-Time Monitoring of Cell Apoptosis and Self-Evaluating of Pro-Apoptotic Theranostics

Bioimaging probes for accurately monitoring apoptosis process have extensive significance for cell biological studies and clinical investigations. Herein, novel multifunctional peptide-tailored gold nanoclusters (AuNCs) have been developed for real-time imaging of caspase-indicated cell apoptosis. The AuNCs nanoprobe was facilely prepared by a one-step peptide-mediated biomineralization with the dye (TRAMA)-tagged peptides specific to caspase 3 as both template agents and the signal switch. Unlike conventional FRET-based fluorescent probes of caspase activity, these nanoprobes relied on the unique quenching effect of AuNCs through the nanosurface energy transfer (NSET) from dye to AuNCs. Intracellular caspase 3 activation cleaved the substrate peptide and released the dye from AuNCs, leading to a significant fluorescence lighting-up for sensitive and continuous analysis of caspase 3 activity in live cells, with a high signal-background ratio, wide linear range (32 pM-10 nM), and ultralow detection limit (12 pM). Moreover, this versatile AuNCs nanoprobe can serve as a theranostic platform via codisplaying pro-apoptotic and detecting peptides, which allows in situ activation and real-time monitoring of apoptosis in cancer cells. These results indicate that the AuNCs nanoprobe provides a smart molecular imaging and therapeutic agent targeted to cell apoptosis, which has great potential for apoptosis-related diagnosis and precision chemotherapy.