Beyond the protein corona - lipids matter for biological response of nanocarriers.

The interaction of nanocarriers with blood plasma components influences the biological response, and therefore, it needs to be controlled. Whereas protein adsorption to nanocarriers has been investigated to a large extent, the role of lipid interaction for drug delivery and its biological effect is not yet clear. However, lipids represent an important constituent of blood plasma and are usually bound in the form of lipoproteins. Because already for many nanocarrier systems an enrichment of apolipoproteins in their protein corona was reported, we examine the interaction of lipoproteins with nanocarriers. If interaction occurs in terms of lipoprotein adsorption, two scenarios are possible: adsorption of intact lipoprotein complexes or disintegration of the complexes with adsorption of the single components. To investigate the interaction and clarify which scenario occurs, polymeric model nanoparticles and different lipoprotein types have been studied by isothermal titration calorimetry, transmission electron microscopy, and other methods. Our data indicate that upon contact with polymeric nanoparticles, disintegration of lipoproteins and adsorption of lipids occurs. Further, the effect of lipoprotein adsorption on cell uptake has been examined, and a major effect of the lipoproteins has been found. It is now well accepted that nanomaterials developed as diagnostic or therapeutic carrier systems need to be well characterized in terms of biological responses inside an organism. Many studies have already shown that proteins adsorb to the surface of a nanomaterial and create a new interface that define the identity of the material. However, the presence of other surface-active components of the blood plasma and how they interact with nanomaterials has been much less investigated. Thus, this study aims at providing a significant contribution to understanding the interaction mechanism between lipoproteins and nanomaterials. Since lipoproteins transport a high amount of lipids, which are surface-active molecules, the demonstrated interactions can go as far as complete lipoprotein disintegration.