Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: in vitro studies on neural tissue cells

Abstract

Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types. PS NPs within a size-range of 45-70 nm influenced the metabolic activity of cells depending on the cell-type, but caused toxicity only at extremely high particle concentrations. Neurons did not internalize particles, while microglial cells ingested a large amount of carboxylated but almost no PEGylated NPs. PEGylation reduced the protein adsorption, toxicity and cellular uptake of NPs. After storage (shelf-life >6 months), the toxicity and cellular uptake of NPs increased. The altered biological activity of "aged" NPs was due to particle aggregation and due to the adsorption of bioactive compounds on NP surfaces. Aggregation by increasing the size and sedimentation velocity of NPs results in increased cell-targeted NP doses. The ready endotoxin adsorption which cannot be prevented by PEG coating, can render the particles toxic. The age-dependent changes in otherwise harmless NPs could be the important sources for variability in the effects of NPs, and could explain the contradictory data obtained with "identical" NPs.

Endotoxin Contamination in Nanomaterials Leads to the Misinterpretation of Immunosafety Results

“…In a study in which NPs synthesis was repeated in normal conditions or after glassware and tool depyrogenation, we could show that taking precautions could significantly dampen the endotoxin contamination in ENM (28). On the other hand, a heavy endotoxin contamination in polystyrene ENM after long-term storage (over 6 months) may have been due to the poor handing processes (29). Thus, we should be aware that endotoxin contamination in ENM is a common phenomenon.…”

Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold nanoparticles, interferes with biocorona formation and induces human monocyte inflammatory activation

“…In previous studies, we showed that different batches of NPs synthesized following an identical protocol may have different contamination levels of endotoxin depending on the level of cleanliness during the synthesis procedure (Oostingh et al 2011). Also, we found that poor handling processes and storage under different conditions can contaminate NPs and endow them with an inflammatory potential (Murali et al 2015). This is a consequence of the fact that LPS can bind to all kinds of surfaces and thus represents a ubiquitous contaminant in all types of biomaterials (Gorbet and Sefton 2005;.…”

Uptake and distribution of ultrafine nanoparticles and microemulsions from the nasal mucosa

“…Similar observations have been reported by other investigators [148][149] , and it has been repeatedly shown that surface chemistry plays an important role in cellular internalization.…”

“…The results reported are inconsistent or unclear regarding whether PEGylation improves the uptake of intact nanoparticles across the epithelial tissues. For example, a study reported that 45 -70 nm polystyrene nanoparticles with PEGylated surfaces showed almost no uptake into microglial cells following 1 h incubation with neural cells whereas carboxylated surface functionalization showed significantly higher uptake into those cells 149 . This result is somewhat in agreement with the findings from presenty study using PEG-QDs administered intranasally in mice, which showed no accumulation in deeper nasal tissues compared to COOH-QDs.…”