Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation

Abstract

The chemical composition, size, shape and surface characteristics of nanoparticles affect the way proteins bind to these particles, and this in turn influences the way in which nanoparticles interact with cells and tissues. Nanomaterials bound with proteins can result in physiological and pathological changes, including macrophage uptake, blood coagulation, protein aggregation and complement activation, but the mechanisms that lead to these changes remain poorly understood. Here, we show that negatively charged poly(acrylic acid)-conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which promotes interaction with the integrin receptor, Mac-1. Activation of this receptor increases the NF-κB signalling pathway, resulting in the release of inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen demonstrated this effect. Our results show that the binding of certain nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more commonly described role of oxidative stress in the inflammatory response to nanomaterials.

The responses of immune cells to iron oxide nanoparticles

“…Similar to the alternation of NP hydrodynamic size, the partial neutralization of NP surface charge may have resulted from the absorption of counter-charged serum proteins on to positively charged NPs (Huhn et al, 2013) and negatively charged NPs (Monopoli et al, 2011). Apart from electrostatic attraction, hydrophobic interactions were also capable of alternating the surface charge of negatively charged NPs, which were recently reported on gold NP systems (Deng et al, 2011;Liu et al, 2013b). Although zeta potentials were partially changed, these NP-medium mixtures were still stable with no NP precipitation in solutions ( Supplementary Fig.…”

“…For example, formation of protein corona decreased colloidal stability of NPs (Liu et al, 2010) and reduced cellular uptake (Bajaj et al, 2009). On the other hand, NPs could alter the conformation of absorbed proteins, leading to activation of particular cell signaling pathways and cytokine releases (Deng et al, 2011). To reduce non-specific protein absorption, neutral coatings are normally used to modify NP surfaces, which create steric hindrance to prevent protein absorption (Verma, 2010).…”

Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface

“…In some cases this seems successful, 3 but in others less so (for example targeting moieties can hinder biological barrier penetration 8,11 ). Practical problems include the fact that surface-grafting of biofunctional moieties may disrupt protein structure and function 21,22 , or constrain its orientation.…”

Improved Biocompatibility of Black Phosphorus Nanosheets by Chemical Modification

“…More importantly, when nanomaterials were accumulated in MPS, concentrated macrophages would inevitably initiate immune responses, and provoke various side effects (such as inflammation), which would also hamper therapeutic efficacy of nanomaterials 10. In recent years, various nanomaterials have been investigated and reported as active foreign particles that can stimulate inflammatory effects when administered to animals or humans 11. Severe or sustained inflammatory responses can lead to diseases due to damages to normal organs or tissues by the stimulated immune cells 12.…”

“…TNF‐α is among the typical cytokines secreted, and are frequently stimulated during the infection of pathogens or foreign particles 11. Because its ATP content was not affected according to previous experiments, raw 264.7 cells were selected to evaluate the proinflammatory activity of BPs by the assessment of TNF‐α release.…”