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

Abstract

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.

Plasmonic SERS Au Nanosunflowers for Sensitive and Label-Free Diagnosis of DNA Base Damage in Stimulus-Induced Cell Apoptosis

“…Similarly, the RSD values of SERS intensity at the three bands for genomic DNAs extracted from HCT-116 cells were estimated to be 18.67, 10.86, and 19.01%, respectively. These results indicated that the Au nanosunflowers had good reproducibility and accuracy for SERS detection, which could meet the requirement of SERS detection with RSD value less than 20% . To further prove the repeatability of Au nanosunflowers for SERS detection of different samples under the same condition, six samples of genomic DNAs extracted from HCT-116 cells before ES were also performed for SERS detection.…”

“…Recently, we found that the ES treatment at constant ∼1.2 V for 5 min causes severe damage on cancerous cells while it is almost harmless to normal healthy cells. − However, the therapeutic impacts of ES on cellular DNAs, on their base level, are still unknown. Prior to SERS probing using the Au nanosunflowers, we first amply examined the therapeutic response difference of cancerous cells and normal cells on ES by choosing eight different types of cell lines.…”

“…They also monitored the reactive oxygen species-induced DNA damage for cancer cells by using a label-free SERS technique . Our previous work showed that electrical stimulation (ES) at a low applied voltage (∼1–3 V) was sufficient to selectively kill cancerous cells in vitro or in vivo. − Nevertheless, the therapeutic impacts of ES on cellular DNAs, especially at their base level, are still unknown and remain a basic challenge in the field.…”

Sodium alginate and naloxone loaded macrophage-derived nanovesicles for the treatment of spinal cord injury

“…Moreover, Bax and Bcl-2 are a pair of key regulatory factors with opposite functions in apoptosis [ 49 , 50] . The increase in Bax, Caspase-3, and Bax/Bcl-2 indicated an increased proportion of neuronal apoptosis after SCI [51] . The increase in the anti-apoptotic factor (Bcl-2) could alleviate the level of neuron apoptosis.…”

Electrostimulus-associated PD-L1 expression on cell membrane revealed by immune SERS nanoprobes

“…13,14 Jin's studies used the ES method to realise the release of cytochrome c, activation of caspase-3 and exteriorisation of phosphoserine to accelerate cell apoptosis. [15][16][17] Compared with drug treatments, ES is a fast and controlled method that can avoid the shortcomings of chemical drugs, which require a long period and have uncontrollable side effects when exogenous matter enters the cells. However, the impacts of ES on the dynamic expression of PD-L1 have not been revealed.…”