Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles
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Polymeric nanoparticles (PNPs) are a promising platform for drug, gene, and vaccine delivery. Although generally regarded as safe, the toxicity of PNPs is not well documented. The present study investigated in vitro toxicity of poly-?-caprolactone, poly(DL-lactic acid), poly(lactide-cocaprolactone), and poly(lactide-co-glycide) NPs and possible mechanism of toxicity. The concentration-dependent effect of PNPs on cell viability was determined in a macrophage (RAW 264.7), hepatocyte (Hep G2), lung epithelial (A549), kidney epithelial (A498), and neuronal (Neuro 2A) cell lines. PNPs show toxicity at high concentrations in all cell lines. PNPs were efficiently internalized by RAW 264.7 cells and stimulated reactive oxygen species and tumor necrosis factor-alpha production. However, reactive nitrogen species and interleukin-6 production as well as lysosomal and mitochondrial stability remained unaffected. The intracellular degradation of PNPs was determined by monitoring changes in osmolality of culture medium and a novel fluorescence recovery after quenching assay. Cell death showed a good correlation with osmolality of culture medium suggesting the role of increased osmolality in cell death. ? The Author 2013. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.