Characterization and Applications of the Protein Corona Forming on the Naturally Occurring Nanoparticles, Low-Density Lipoproteins

Abstract Low-density lipoproteins (LDL) are naturally occurring, monodisperse nanoparticles composed of proteins and lipids with an average diameter of 18–25 nm. Their biological functions such as cholesterol trafficking and their role in various diseases have been extensively studied. However, their properties as nanoparticles are seldom discussed. Here, we show that when isolated from biofluids, analogous to any synthetic nanoparticle, LDL carry a distinctive protein corona. The corona can be partly removed or preserved depending on the approach used to isolate them. Importantly, we find that proteomic analysis of this corona enables proof-of-concept separation between healthy individuals and patients with melanoma, colon carcinoma, or liver cancer. This approach provided clearer separation than direct proteomic analysis of serum because the corona of the LDL particle is relatively depleted of the serum-abundant proteins, most of which are only minor components of the corona. We postulate that proteomic analysis of lipoproteins can reveal disease-associated changes and that a deep understanding of the corona of these particles will advance the overall field of nanoparticles in medicine.