Background and Aims: Coated nanoparticles have different surface chemistry, aggregation, and interaction properties. The aim of this study was to investigate the cytotoxicity of silver nanoparticles AgNPs coated with different proteins on Balb/c macrophages.

Materials and Methods: In this study these items were evaluated: 1) the size of aggregation, 2) the quantity and mechanisms of uptake, and 3) the biological impact of Ag NPs and protein coated Ag NPs. Human serum albumin, bovine serum albumin, fetal calf serum, and pea nut agglutinin were used as coating agents.

Results: This research showed that all coated Ag NPs had smaller aggregate size, more uptake, and less biological impact on Balb/c macrophages than naked Ag NPs. Endocytosis mediated pathway was the main uptake mechanism. Also, a clathrin-mediated pathway was shown to regulate their uptake.

Conclusions: It can be concluded that mitochondrial activities, cellular metabolic function, and ATP level of cells treated with protein coated Ag NPs are higher than naked Ag NPs after 24-hour incubation.