Interactions of Apolipoproteins with Lipid-Based Nanoparticles

Serum proteins bind and form a dynamic protein corona around nanoparticles (NPs) that have been injected into the mammalian vasculature. Several fundamental studies have shown that apolipoproteins are prominent components of the NP corona. Since apolipoproteins control the distribution of lipoproteins, they may also control the distribution of NPs. Indeed, apolipoprotein affinity for NPs has been recently taken advantage of to deliver CRISPR reagents encapsulated in NPs to cells that express particular lipoprotein receptors. In this scenario, an apolipoprotein binds an NP and the resulting apolipoprotein-NP complex binds a cell that expresses the (apo)lipoprotein receptor. But the NP will be diverted from the target cell if it does not express the (apo)lipoprotein receptor. This may hamper NP treatment of diseases. Therefore, we must understand the kinetics of apolipoprotein-NP affinity and how apolipoprotein-NP interactions affect NP biodistribution. In this Perspective, we discuss the evolving topic of apolipoproteinNP interactions, which is of great interest for all NP-based disease treatments. Many properties of apolipoprotein-NP complexes are yet to be determined and will have a significant impact on NP efficacy for many NP-based treatments in animal models and in the clinic.