Unraveling the impact of different liposomal formulations on the plasma protein corona composition might give hints on targeting capability of nanoparticles

Abstract

Nanoparticles (NPs) interact with biological fluids after being injected into the bloodstream. The interactions between NPs and plasma proteins at nano-bio interface affect their biopharmaceutical properties and distribution in the organ and tissues due to protein corona (PrC) composition, and in turn to modification of the resulting targeting capability. Moreover, lipids and polymers of NPs, at their interface, affect the composition of PrC and the relative adsorption and abundance of specific proteins. To investigate this latter aspect, we synthesized and characterized different liposomal formulations (LFs) with lipids and polymer-conjugated lipids, at different molar ratios, having different sizes, size distributions and surface charges. The PrC composition of various designed LFs was evaluated ex vivo in human plasma by label-free quantitative proteomics. We also correlated the relative abundance of identified specific proteins in the coronas of the different LFs, with their physicochemical properties (size, PDI, zeta potential). The evaluation of outputs from different bioinformatic tools discovered protein clusters allowing to highlight: i) the common as well as the unique species for the various formulations; ii) the correlation between each identified PrC and the physicochemical properties of LFs; iii) some preferential binding determined by physicochemical properties of LFs; iv) the occurrence of formulation-specific protein patterns in PrC. Investigating specific clusters in PrC will help to decode the multivalent roles of the protein pattern components in the drug delivery process, taking advantage from the bio-nanoscale recognition and identity for significant advances in nanomedicine.