Nanoparticle Ligand-Decoration Procedures Affect in Vivo Interactions with Immune Cells

Ligand-decorated nanoparticles are extensively studied and applied for in vivo drug delivery and molecular imaging. Generally, two different ligand-decoration procedures are utilized; ligands are either conjugated with nanoparticle ingredients and incorporated during nanoparticle preparation, or they are attached to preformed nanoparticles by utilizing functionalized reactive surface groups (e.g., maleimide). Although the two procedures result in nanoparticles with very similar physicochemical properties, formulations obtained through the latter manufacturing process typically contain nonconjugated reactive surface groups. In the current study, we hypothesized that the different ligand-decoration procedures might affect the extent of interaction between nanoparticles and immune cells (especially phagocytes). In order to investigate our hypothesis, we decorated lipidic nanoparticles with a widely used cyclic Arg-Gly-Asp (cRGD) peptide using the two different procedures. As proven from in vivo experiments i...