Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics

• Published in: Nature communications Vol. 8; no. 1; pp. 777 - 8
• Main Authors: Bertrand, Nicolas, Grenier, Philippe, Mahmoudi, Morteza, Lima, Eliana M., Appel, Eric A., Dormont, Flavio, Lim, Jong-Min, Karnik, Rohit, Langer, Robert, Farokhzad, Omid C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-10-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154/152; 631/154/433; 639/925/352/152; Adsorption; Animals; Apolipoproteins; Apolipoproteins - metabolism; Biomolecules; Blood circulation; C3 protein; Complement Activation; Complement C3 - genetics; Complement C3 - metabolism; Complement component C3; Drug Delivery Systems; Humanities and Social Sciences; Hydrophobic and Hydrophilic Interactions; Incubation; Libraries; Male; Mice; Mice, Knockout; multidisciplinary; Nanomaterials; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanotechnology; Particle Size; Pharmacokinetics; Pharmacology; Physicochemical properties; Polyethylene glycol; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Protein Corona - metabolism; Rats; Rats, Sprague-Dawley; Receptor density; Receptors, LDL - metabolism; Science; Science (multidisciplinary); Surface Properties
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-00600-w

In vitro incubation of nanomaterials with plasma offer insights on biological interactions, but cannot fully explain the in vivo fate of nanomaterials. Here, we use a library of polymer nanoparticles to show how physicochemical characteristics influence blood circulation and early distribution. For particles with different diameters, surface hydrophilicity appears to mediate early clearance. Densities above a critical value of approximately 20 poly(ethylene glycol) chains (MW 5 kDa) per 100 nm
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prolong circulation times, irrespective of size. In knockout mice, clearance mechanisms are identified for nanoparticles with low and high steric protection. Studies in animals deficient in the C3 protein showed that complement activation could not explain differences in the clearance of nanoparticles. In nanoparticles with low poly(ethylene glycol) coverage, adsorption of apolipoproteins can prolong circulation times. In parallel, the low-density-lipoprotein receptor plays a predominant role in the clearance of nanoparticles, irrespective of poly(ethylene glycol) density. These results further our understanding of nanopharmacology.
Understanding the interaction between nanoparticles and biomolecules is crucial for improving current drug-delivery systems. Here, the authors shed light on the essential role of the surface and other physicochemical properties of a library of nanoparticles on their in vivo pharmacokinetics.