Effects of Protein Source on Liposome Uptake by Cells: Corona Composition and Impact of the Excess Free Proteins

Corona formation in biological fluids strongly affects nanomedicine interactions with cells. However, relatively less is known on additional effects from the free proteins in solution. Within this context, this study aims to gain a better understanding of nanomaterial-cell interactions in different biological fluids and, more specifically, to disentangle effects due to corona composition and those from the free proteins in solution. To this aim, the uptake of liposomes in medium with bovine and human serum are compared. Uptake efficiency in the two media differs strongly, as also corona composition. However, in contrast with similar studies on other nanomaterials, despite the very different corona, when the two corona-coated liposomes are exposed to cells in serum free medium, their uptake is comparable. Thus, in this case, the observed differences in uptake depend primarily on the presence and source of the free proteins. Similar results are obtained when testing the liposomes on different human cells, as well as in murine cells and in the presence of murine serum. Overall, these results show that the protein source affects nanomedicine uptake not only due to effects on corona composition, but also due to the presence and composition of the free proteins in solution.