The Peptide/Antibody‐Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF‐κB Protein Expression in Inflamed Cells In Vitro

Abstract

Earlier studies with nanoparticles carrying siRNA were restricted to investigating the inhibition of target‐specific protein expression, while almost ignoring effects related to the nano-particle composition. Here, we demonstrate how the design and surface decoration of nanoparti-cles impact the p65 nuclear factor‐kappa B (NF‐κB) protein expression in inflamed leucocytes and endothelial cells in vitro. We prepared silica‐coated calcium phosphate nanoparticles carrying encapsulated siRNA against p65 NF‐κB and surface‐decorated with peptides or antibodies. We show that RGD‐decorated nanoparticles are efficient in down‐regulating p65 NF‐κB protein expression in endothelial cells as a result of an enhanced specific cellular binding and subsequent uptake of nanoparticles. In contrast, nanoparticles decorated with IgG (whether specific or not for CD69) are efficient in down‐regulating p65 NF‐κB protein expression in T‐cells, but not in B‐cells. Thus, an optimized nanoparticle decoration with xenogenic IgG may stimulate a specific cellular uptake. In summary, the composition of siRNA‐loaded calcium phosphate nanoparticles can either weaken or stimulate p65 NF‐κB protein expression in targeted inflamed leucocytes and endothelial cells. In general, unveiling such interactions may be very useful for the future design of anti‐p65 siRNA‐based nanomedicines for treatment of inflammation‐associated diseases.