Effect of Au@SiO₂ core shell nanoparticles on HG-induced oxidative stress triggered apoptosis in keratinocytes

Growing evidences suggest that excess generation of highly reactive free oxygen/nitrogen radicals (ROS/RNS) are largely due to hyperglycemia causes oxidative stress. Further, excess accumulation of ROS/RNS in cellular compartments aggravates the development and progression of diabetes and its associated complications. Impaired wound healing in diabetic condition is a known vital complication all around the world. Thus, an antioxidant agent having the potential for hindering the oxidative/nitrosative stress triggered diabetic skin complication is required. The present investigation was carried out to understand the impact of silica coated gold nanoparticle (Au@SiO₂ NPs) on high glucose (HG)-induced keratinocyte complications. We demonstrated that HG environment enhanced the ROS and RNS accumulations and reduced in cellular antioxidant capacities in keratinocte cells, however, Au@SiO₂ NPs treatment restored the HG effect. Furthermore, excess production of ROS/RNS was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm), and increased in mitochondrial mass, which was restored by Au@SiO₂ NPs treatment in keratinocyte cells. In addition, HG-induced excess production of ROS/RNA caused an increased in the biomolecules damage including lipid peroxidation (LPO), and protein carbonylation (PC), 8-oxoguanine DNA glycosylase-1 (OGG1) expression and increased 8-hydroxydeoxyguanosine (8-OHdG) accumulations in DNA, leading to activation of ERK1/2MAPK, AKT and tuberin pathway, inflammatory reaction, and finally apoptotic cell death. In conclusion, our findings showed that Au@SiO₂ NPs treatment improved the HG-induced keratinocytes injury by suppressing the oxidative/nitrosative stress, elevating the antioxidant defence system, thereby inhibiting the inflammatory mediators and apoptosis, which may be a therapeutic cure for the diabetic keratinocyte problems.