Smart and NoninvasiveSERS Immunosensors for MonitoringDynamic Expression of Cytokines during Cell Pyroptosis

Accompanying the occurrence of inflammatory reaction to release cytokines, pyroptosis can activate an immune response for resistance against cancer. Consequently, elevated levels of cytokines released by cancer cells are highly correlated with the effectiveness of cancer treatment. Herein, a noninvasive surface-enhanced Raman spectroscopy (SERS) immunosensor was developed to sensitively and specifically measure the tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, during the cell pyroptosis process. The sandwiched structure of the sensor is functionalized with a TNF-α binding antibody for detecting TNF-α at concentrations as low as 1 pg/mL. Importantly, electrical stimulation (ES) can fleetly trigger cancer cell pyroptosis to induce the overexpression of receptor interacting protein 3 (RIP3), which is a significant protein that regulates the inflammatory response. The overexpression of RIP3 can activate caspase-1 to promote the upregulation of cytokine levels. Notably, the cytokine levels of TNF-α released from cancer cells (MCF-7 cells) were apparently higher than those of normal cells (MCF-10A cells) during pyroptosis detected by the SERS immunosensors. Due to its obvious superiorities of simple fabrication and fast readout without sample pretreatment, the developed SERS platform has a potential application value for diagnosis and treatment of cancer.