Stealth Effect of Biomolecular Corona on Nanoparticle Uptake by Immune Cells

Abstract

When injected in a biological milieu, a nanomaterial rapidly adsorbs biomolecules forming a biomolecular corona. The biomolecular corona changes the interfacial composition of a nanomaterial giving it a biological identity that determines the physiological response. Characterization of the biomolecular structure and composition has received increasing attention mostly due to its detrimental impact on the nanomaterial's metabolism in vivo. It is generally accepted that an opsonin-enriched biomolecular corona promotes immune system recognition and rapid clearance from circulation. Here we applied dynamic light scattering and nanoliquid chromatography tandem mass spectrometry to thoroughly characterize the biomolecular corona formed around lipid and silica nanoparticles (NPs). Incubation with human plasma resulted in the formation of NP-biomolecular coronas enriched with immunoglobulins, complement factors, and coagulation proteins that bind to surface receptors on immune cells and elicit phagocytosis. Conversely, we found that protein-coated NPs were protected from uptake by macrophage RAW 264.7 cells. This implies that the biomolecular corona formation provides a stealth effect on macrophage recognition. Our results suggest that correct prediction of the NP's fate in vivo will require more than just the knowledge of the biomolecular corona composition. Validation of efficient methods for mapping protein binding sites on the biomolecular corona of NPs is an urgent task for future research.

<div>Effects of the protein corona on liposome&ndash;liposome and liposome&ndash;cell interactions</div>

“…For several decades, cell opsonization was considered the body's first defense mechanism against foreign entities, 47 but recent studies have shown that the PC can shield particles from the action of adsorbed serum components (IgG and complement factors) that normally favor particle clearance. 19,20 Here we report increased liposome uptake by both J774 and 4T1 cells after plasma incubation. We hypothesize that complement factors and apolipoproteins present in the PC are mainly responsible for this effect.…”

“…18 However, in a recent study, unfolded proteins that promote macrophage uptake or their shielding by other proteins in the PC were found to reduce in vitro particle uptake by RAW264.7 macrophages. 19,20 The particular context, therefore, needs to be discussed when considering cellular uptake. Although the biological identity of NPs largely determines their biological fate, their physical identity (ie, shape, size, and surface charge) strictly regulates NP-cell interactions.…”

Buoyant Nanoparticles: Implications for Nano‐Biointeractions in Cellular Studies

“…In line with these observations, another study moreover clearly demonstrated that the protein corona formed from serum or lung lining fluid decreased the cytotoxic and hemolytic activity of functionalized polymeric nanoparticles, suggesting that the protein corona can provide protection in nano‐biointeractions. Other studies have also noted that the composition of the protein corona can affect recognition and subsequent uptake of particles by target cells . Recent advances in measuring particle–cell interactions in real time have further underscored the significance of the protein corona in nano‐safety assessments…”

“…The role of intrinsic properties of nanoparticles such as size, [ 31 ] shape, crystallinity, charge [ 32 ] on biointeractions is well established in the literature. [ 33,34 ] Similarly, the importance of the protein coronas on bioactivity is well recognized. [ 35,36 ] The fundamental rule of toxicology is that the "dose makes the poison".…”

Nanoparticles and direct immunosuppression

“…[23][24][25] However, the inherent immunological response to nanomaterials may be also exploited for novel therapies. Immunological response can be modulated and suppressed through multiple pathways by the engineering the physiochemical properties of the nanomaterials.…”