Colloidal Stability and Surface Chemistry Are Key Factors for the Composition of the Protein Corona of Inorganic Gold Nanoparticles

Abstract

To study the influence of colloidal stability on protein corona formation, gold nanoparticles are synthesized with five distinct surface modifications: coating with citric acid, bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt, thiol-terminated methoxy-polyethylene glycol, dodecylaminegrafted poly(isobutylene-alt-maleic anhydride), and dodecylamine-grafted poly(isobutylene-alt-maleic anhydride) conjugated with polyethylene glycol. The nanoparticles are incubated with serum or bronchoalveolar lavage fluid from C57BL/6 mice (15 min or 24 h) to assess the effect of differential nanoparticle surface presentation on protein corona formation in the air-blood barrier exposure pathway. Proteomic quantification and nanoparticle size measurements are used to assess protein corona formation. We show that surface modification has a clear effect on the size and the composition of the protein corona that is related to the colloidal stability of the studied nanoparticles. Additionally, differences in the composition and size of the protein corona are shown between biological media and duration of exposure, indicating evolution of the corona through this exposure pathway. Consequently, a major determinant of protein corona formation is the colloidal stability of nanoparticles in biological media and chemical or environmental modification of the nanoparticles alters the surface presentation of the functional epitope in vivo. Therefore, the colloidal stability of nanoparticles has a decisive influence on nano-bio interactions.

Cytotoxicity-Related Bioeffects Induced by Nanoparticles: The Role of Surface Chemistry

“…For example, compared to mercaptosuccinic acid and N-4thiobutyroil glucosamine, PEG 5000 and alkyl-PEG 600 decorations on GNPs (14-22 nm) induced lower levels of protein adsorption from FBS (Silvestri et al, 2017). In another comparative study, PEG-GNPs (5 nm) were found to adsorb fewer proteins than were adsorbed by citric-, phosphine-, or poly(isobutylene-altmaleic anhydride)-GNPs (Johnston et al, 2017). Moreover, PEG decoration on GNPs (13 nm) was also found to bind fewer proteins than were bound by the tannic acid decoration (Braun et al, 2016).…”

The Crown and the Scepter: Roles of the Protein Corona in Nanomedicine

“…Xu et al have used the hierarchical cluster (HCA) analysis to analyze the relation of physiochemical parameters determined protein corona and biological effects. The hydrodynamic radii, in vitro uptake and in vivo biodistribution of NPs seems to be indirectly driven by the protein corona, which is determined by the physiochemical properties of NPs, especially, including colloidal stability and surface chemistry …”

Biological Behavior Regulation of Gold Nanoparticles via the Protein Corona

“…[ 15,18 ] The total number of identified proteins around GNPs was dramatically different after they were incubated with the murine blood serum (209 proteins) and murine bronchoalveolar lavage fluid (503 proteins), respectively. [ 30 ] Meanwhile, the top protein species were also different. Complement component 3 (C3), albumin (Alb), and fibronection (FN1) were the top three proteins after 15 min incubation of the murine blood serum, while for the murine bronchoalveolar lavage fluid group the top three proteins changed into indolethylamine N ‐methyltransferase (Inmt), Alb, and SEC14‐like 13 (Sec1413).…”

“…Other environmental parameters that affect the PC nature include the incubation time, temperature, and concentration of plasma/serum proteins. The amount of top‐ranked proteins in the PC of GNPs incubated with the mouse serum for 24 h changed markedly compared to those for 15 min incubation, [ 30 ] indicating the evolution of the PC with increased incubation time. Moreover, the incubation temperature also affected the PC composition and this effect was quite different between in vitro and in vivo.…”

“…The PC formed on GNPs with five distinct surface modifications in murine serum clarified the direct effect of the surface modifier on the PC composition. [ 30 ] GNP‐citric and GNP‐phosphine absorbed more complement C3 (> 40% vs Alb ≈ 15%). While the polymer‐coated GNPs, i.e., GNP‐PEG‐SH, GNP‐PMA (GNPs modified by poly(isobutylene‐alt‐maleic anhydride), and GNP‐PMA‐satPEG (amino terminated methoxy‐PEG covalently attached to the surface of GNP‐PMA) absorbed less complement C3 (10–20%).…”