Technical challenges of studying the impact of plasma components on the efficacy of lipid nanoparticles for vaccine and therapeutic applications

Abstract

Recently, Liu et al. 1 . suggested to use magnetic beads coated with PEG-antibodies to pull down and isolate clinically relevant pegylated lipid nanoparticles (LNPs) from plasma. In principle, this method solves one of the major hurdles in the study of interactions between lipid-based nanometer-sized delivery systems for therapeutic use and blood constituents, namely co-isolation of similarly sized endogenous nanoparticles (NPs) with surface lipids including lipoproteins and extracellular vesicles (EVs). The interaction between exogenous lipid-based NPs and plasma constituents is believed to dictate the fate and, thus, the therapeutic efficacy and toxicity of these products. For these reasons, much effort is put into improving the study of the biomolecule adsorption to NPs. Here, I question whether the pull-down method proposed by Liu et al. indeed avoids the co-isolation of lipoproteins and EVs. My main concern is the inherent propensity of the labile pegylated-lipid, DMPE-PEG, incorporated into their LNPs to dissociate and become embedded into the surface of endogenous NPs. This type of dynamic may potentially pose a great challenge to affinity-based isolation methods. With that in mind, I discuss some of the data and conclusions presented by Liu et al.

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