Colloidal silver nanoparticles improve anti-leukemic drug efficacy via amplification of oxidative stress

•AgNPs were prepared by a continuously flow electrochemical process.•AgNPs could localize in lysosomes, mitochondria and cytoplasm of SHI-1 cells.•AgNPs together with 4-HPR showed the synergistic inhibition against SHI-1 cells.•AgNPs combined with 4-HPR induced the higher levels of ROS compared to that alone.•Silver ions were released from AgNPs in lysosome-like acidic conditions. Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy.