Effect of liposome rigidity on corona formation and its implications for uptake by cells

Abstract Nanoparticle rigidity influences cellular uptake and in vivo behavior, yet the underlying mechanisms remain unclear. Here we used lipids with identical head groups but different acyl chains to prepare liposomes with comparable surface composition, size and zeta potential, but distinct mechanical properties. Rigid liposomes showed much higher uptake than soft ones, mediated by distinct endocytic mechanisms. Proteomic analysis revealed that rigid and soft liposomes adsorbed very different coronas upon dispersion in serum. RNA interference and competition studies indicated that the enhanced uptake of rigid liposomes is likely driven by the lower abundance of multiple apolipoproteins in their corona, and possibly the higher abundance of apolipoprotein H and of a pattern of low-abundant corona proteins. Importantly, a strong difference in uptake was observed only when liposomes were added to cells in the presence of serum. Hence, the different uptake efficiency is not solely due to the different mechanical properties, but results from the effect of liposome mechanical properties on corona formation.