Phycocyanin-Functionalized Selenium Nanoparticles Reverse Palmitic Acid-Induced Pancreatic β Cell Apoptosis by Enhancing Cellular Uptake and Blocking Reactive Oxygen Species (ROS)-Mediated Mitochondria Dysfunction

Accumulation of palmitic acid (PA) in human bodies could cause damage to pancreatic β cells and lead to chronic diseases by generation of reactive oxygen species (ROS). Therefore, it is of great significance to search for nutrition-available agents with antioxidant activity to protect pancreatic islet cells against PA-induced damage. Phycocyanin (PC) and selenium (Se) have been reported to have excellent antioxidant activity. In this study, PC-functionalized selenium nanoparticles (PC-SeNPs) were synthesized to investigate the in vitro protective effects on INS-1E rat insulinoma β cells against PA-induced cell death. A potent protective effect was achieved by regulation of particle size and PC content. Among three PC-SeNPs (165, 235, and 371 nm), PC-SeNPs-235 nm showed the highest cellular uptake and the best protective activities. For cell cycle analysis, PC-SeNPs showed a better protective effect on PA-induced INS-1E cell apoptosis than PC or SeNPs, and PC-SeNPs-235 nm exhibited the best effect. Further mechanistic studies demonstrated that PA induced overproduction of intracellular ROS, mitochondria fragmentation, activation of caspase-3, -8, and -9, and cleavage of PARP. However, pretreatment of the cells with PC-SeNPs effectively blocked these intracellular events, which suggests that PC-SeNPs could protect INS-1E cells against PA-induced cell apoptosis via attenuating oxidative stress and downstream signaling pathways. This finding provides a great promising nutritional approach for protection against diseases related to islet damage.