Fast Activation and Tracing of Caspase-3 Involved Cell Apoptosis by Combined Electrostimulation and Smart Signal-Amplified SERS Nanoprobes.

Caspase-3 is considered as one of the key proteases that can spontaneously regulate the life activities of cells, and its activation (usually is a slow process) will execute the apoptosis process of cells. Rapid activation of caspase-3 on demand in living-cells is therefore highly desired toward precise cancer therapy but it is still a key challenge. Herein, we applied electrostimulus (ES) to achieve fast activation of caspase-3 and trigger cell apoptosis, and developed a smart magnetic-plasmonic assembly nanoprobes (A-nanoprobes) to real-time trace cellular caspase-3 activation at the single cell level. The designer core-satellite A-nanoprobe, working specific to the activated caspase-3 via a disassembly tactic, provides strong "hot spots" to improve the sensitivity and therefore enables SERS sensing of cellular caspase-3 upon activated by ES. Single-cell analysis revealed that the ES can rapidly activate the apoptosis pathway of caspase-3 on demand to make the DNA fragmentation and ultimately induce the cell apoptosis. Such method and nanoplatform were further used to monitor ES-triggered caspase-3 activation in cell apoptosis process of different cell types, revealing that more caspase-3 will be activated for cancerous cells than normal cells during the ES to induce cells apoptosis. This strategy and platform are promising for detecting cellular caspase-3 and other enzymes in the process of cancer diagnosis and treatments.