Particle and nanoparticle interactions with fibrinogen: the importance of aggregation in nanotoxicology

Abstract

Ingested, inhaled or injected particles come into contact with biological fluids containing polymers, such as the protein fibrinogen. We studied interactions between well-characterized submicron particles or nanoparticles (NPs) and human fibrinogen. In vitro aggregation and zeta potential measurements of different sized and functionalized polystyrene, carbon black and silica NPs suspended in fibrinogen solutions were made. Particle size, surface charge and aggregation behaviour significantly changed in the presence of fibrinogen. Polymer (protein) bridging and bridge flocculation was observed. We concluded: (1) NP aggregation rate in a fibrinogen solution depended on particle surface type; (2) amine-functionalized particles aggregated more slowly in fibrinogen; and (3) particle morphology strongly influenced biologically available surface for protein attachment, but this did not correlate well with particle surface area for complex particles (calculated or measured). Interaction of particles and NPs with pro-coagulant polymers may therefore dictate the NP surface dose presentation to cells/organs and subsequent cellular effects, in and ex vivo.

Keywords::

• Nanotoxicology
• particle toxicology
• mechanistic toxicology

Author contributions

MK developed the concept. MK and PD designed the experiments. PD prepared the materials and conducted the DLS measurements. MK, PD and KK jointly interpreted and synthesized the data to form the manuscript. MK, PD and KK jointly revised the manuscript critically for important intellectual content.

Declaration of interest : This work was funded under the Joint Environment and Human Health programme, funded by agencies of the UK Government: The Natural Environment Research Council (NERC) (NERC-EPSRC Project NE-E009395-1. Sept 2007–Dec 2008), Department for Environment Food and Rural Affairs (Defra), Environment Agency (EA), Ministry of Defence (MOD) and the Medical Research Council (MRC). The authors report no conflicts of interest or any competing financial interests. The authors alone are responsible for the content and writing of the paper.