Updated project metadata. In this study, we compared the effects of silver and platinum NPs on the main components of the blood brain barrier model: human cerebral microvascular endothelial cells (hCMEM/D3) and human primary astrocytes under single and co-exposure NP conditions. The co-exposure to two types of NPs synergistically inhibited proliferation of both cell types with the greater extent observed for endothelial cells (the combination index (CI) values for all tested concentrations were below 0.2 corresponding to strong or extreme synergism). In addition, NP-induced toxicity demonstrated dependence on the cell type with astrocytes being more tolerant to the metal NPs. The mechanism of synergy was further explored with short-time incubation time points (up to 30 min), where the cell metabolic activity was decreased to approximately 60% of the controls. The data obtained from the proteomics analysis suggests immunosuppression and deregulation of the extracellular matrix organization as well as contribution of the p75NTR-associated cell death executor (NADE)-dependent apoptotic mechanism in the synergistic cytotoxicity of NPs.