Dimethyl Fumarate Augments Anticancer Activity of Ångstrom Silver Particles in Myeloma Cells through NRF2 Activation

Multiple myeloma (MM) is an incurable hematological malignancy characterized by relapse and drug resistance. This study investigates the potential of angstrom-scale silver particles (F-Ag & Aring;Ps) to selectively target and eliminate MM cells, focusing on their susceptibility and underlying mechanisms. F-Ag & Aring;Ps are synthesized using a pure physical high-efficiency evaporation-condensation method and coated with fructose, and their cytotoxic effects on MM cell lines are evaluated through cell viability assays and flow cytometry. Reactive oxygen species (ROS) levels are measured to elucidate oxidative stress, while the role of nuclear factor erythroid 2-related factor 2 (NRF2) is examined via western blotting and quantitative PCR. In vivo, the therapeutic potential of F-Ag & Aring;Ps is assessed using a MM xenograft mouse model. F-Ag & Aring;Ps exhibited significant cytotoxicity in MM cells at low concentrations, with higher ROS levels leading to oxidative damage and NRF2 accumulation. This effect is mitigated by the ROS scavenger N-acetyl-l-cysteine. Additionally, the NRF2 activator dimethyl fumarate (DMF) enhanced F-Ag & Aring;Ps-induced cytotoxicity in vitro and suppressed myeloma growth in vivo. These findings suggest that combining DMF with F-Ag & Aring;Ps is a promising therapeutic strategy for MM, effectively targeting ROS-induced oxidative damage through NRF2 activation.