Prevention of Dominant IgG Adsorption on Nanocarriers in IgG‐Enriched Blood Plasma by Clusterin Precoating

Abstract

Nanocarriers for medical applications must work reliably within organisms, independent of the individual differences in the blood proteome. Variation in the blood proteome, such as immunoglobulin levels, is a result of environmental, nutrition, and constitution conditions. This variation, however, should not influence the behavior of nanocarriers in biological media. The composition of the protein corona is investigated to understand the influence varying immunoglobulin levels in the blood plasma have on the interactions with nanocarriers. Specifically, the composition of the nanocarriers' coronas is analyzed after incubation in plasma with normal or elevated immunoglobulin G (IgG) levels, and cellular uptake is monitored in cell lines containing different immunoglobulin receptors. Here, it is reported that upon doubling the IgG concentration in plasma, the IgG fraction in the protein corona increases by a factor of 40 independent of the nanocarrier material. This results in a significant increase in uptake in cells exhibiting IgG binding receptors. Furthermore, precoating nanocarriers with clusterin successfully prevents dominant IgG‐adsorption and additionally reduces cellular internalization, after incubation with IgG‐enriched plasma. Therefore, precoating nanocarriers may be utilized as a powerful method to reduce the influence of individual variations in blood composition on the protein corona.

Functionalization of Liposomes with Hydrophilic Polymers Results in Macrophage Uptake Independent of the Protein Corona

“…It was already shown that the plasma composition is subject to individual deviations and additionally differs between healthy donors and diseased patients, leading to a “personalized protein corona”. 53−56 This means that by reducing the overall influence of the protein corona, the complications introduced by personalization effects could also be potentially minimized.…”

Isothermal titration calorimetry as a complementary method for investigating nanoparticle–protein interactions

“…1 and in Table 1. 8 Remaining questions in the field include (but are not limited to) the possibility of protein-multilayers in the corona, 17,18 the exact mechanism of the Vroman effect with influence of kinetics on the protein corona, 10,19,20 and the thermodynamics of specific NP-protein interactions. 21 For these open questions, the thermodynamic information obtainable with ITC can be of significant aid by offering a strong complementary method to the analytical toolbox of protein corona research.…”

Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake

“…For instance, both IgG and albumin prefer binding to the NPs with strongly basic (NH 2 ) or weakly acidic (COOH) groups [92]. Due to the effect of IgG among other proteins on particle removal from the blood, its adhesion to the surface of NPs influences the in vivo cellular fate of NPs [93].…”