Hypoxia- and glutathione-responsive polymer nanoparticles for treating normoxic and hypoxic cancer cells

Malignant tumors display several metabolic characteristics that differ from those of normal tissues. Although these characteristics contribute to aggressive tumor progression, they also offer potential strategies for targeting and treating cancer cells. In this study, we prepared crosslinked polymer nanoparticles (CLPNPs) to encapsulate two hydrophobic drugs, chrysin and ceramide, which are responsive to both hypoxia and glutathione (GSH). The morphology of the CLPNPs was spherical with a particle diameter of 160 nm and a monodisperse distribution. The CLPNPs exhibited hypoxia- and GSH-dependent size changes and drug release, selectively inducing cell death in H1299 cancer cells but not in L929 normal cells. The CLPNPs showed higher cytotoxicity toward H1299 cancer cells under hypoxic conditions than normoxic conditions because of hypoxia-triggered drug release. These results demonstrate that CLPNPs are suitable drug carriers for treating both normoxic and hypoxic cancer cells.