The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs)\nshows great potential for intracellular delivery of DNA. Currently, its application is limited due\nto the potential toxicity and unknown long-term side effects. In this study NPs prepared using a\nbiodegradable polymer, poly(lactic-co-glycolic acid (PLGA) in association with a CPP, was assessed\non two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and\nnormal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular\ninternalization. No effects were observed on the mitochondrial activity and membrane integrity.\nCells exposed to the NPs-DNA-CPP showed low inflammatory response, low levels of apoptosis and\nno activation of caspase-3. Increase in necrotic cells (between 10%-15%) after 24 h of incubation and\nincrease in autophagy, induced by NPs-DNA-CPP, are likely to be related to the lysosomal escape\nmechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs-DNA-CPP\nshowed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential\nantioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for\nintracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be\nconducted in other lung-related systems to better understand its potential effects on the lungs.
Loading....