Lipid nanoparticle protein corona (LNP protein corona) (LNP protein corona)

The lipid nanoparticle (LNP) protein corona refers to the dynamic layer of serum and plasma proteins that spontaneously adsorb onto the surface of LNPs upon exposure to physiological fluids (Monopoli et al., 2012). This biological cloak fundamentally alters the LNP's physicochemical properties, determining its biological identity, stability, and interaction with target cells (Cullis and Hope, 2017). A critical component of this corona is Apolipoprotein E (ApoE), which is recruited from the blood and mediates the highly efficient uptake of LNPs into hepatocytes through the low-density lipoprotein receptor (LDLR) pathway (Akinc et al., 2010). While some corona proteins facilitate delivery, others, such as complement factors and immunoglobulins, can act as opsonins that trigger immune recognition and rapid clearance by the mononuclear phagocyte system (Szebeni, 2014). The composition of the corona is influenced by the LNP's surface charge, size, and lipid composition, particularly the presence of PEGylated lipids which aim to reduce protein adsorption (Vanić et al., 2021). Consequently, the protein corona is a primary determinant of the therapeutic index, safety profile, and biodistribution of LNP-encapsulated drugs, including mRNA vaccines and siRNA therapeutics. Understanding the corona is essential for predicting how different patient populations, who may have varying plasma protein profiles, will respond to LNP-based treatments. It also plays a role in the accelerated blood clearance (ABC) phenomenon, where repeated dosing leads to faster removal of the drug from circulation.

Other names

Biomolecular coronaLNP-protein complexPlasma protein coronaHard coronaSoft corona

Apolipoprotein E-mediated LDLR binding, Complement-mediated phagocytosis, Immunoglobulin-mediated opsonization