Surface charge determines the lung inflammogenicity: A study with polystyrene nanoparticles

Abstract

Surface functionalization is a routine process to improve the behavior of nanoparticles (NPs), but the induced surface properties, such as surface charge, can produce differential toxicity profiles. Here, we synthesized a library of covalently functionalized fluorescent polymeric NPs (F-PLNPs) to evaluate the role of surface charge on the acute inflammation and the localization in the lung. Guanidinium-, acetylated-, zwitterionic-, hydroxylated-, PEGylated-, carboxylated- and sulfated-F-PLNPs were synthesized from aminated-F-PLNP. The primary particle sizes were identical, but the hydrodynamic sizes ranged from 210 to 345 nm. Following surface functionalization, the F-PLNPs showed diverse zeta potentials from -41.2 to 31.0 mV, and each F-PLNP showed a single, narrow peak. Pharyngeal aspiration with these eight types of F-PLNPs into rats produced diverse acute lung inflammation, with zeta potentials of the F-PLNPs showing excellent correlation with acute pulmonary inflammation parameters including the percentage of polymorphonuclear leukocytes (R(2) = 0.90, p < 0.0001) and the levels of interleukin-1β (R(2) = 0.83, p < 0.0001) and of cytokine-induced neutrophil chemoattractant-3 (R(2) = 0.86, p < 0.0001). These results imply that surface charge is a key factor influencing lung inflammation by functionalized polymeric NPs, which further confirms and extends the surface charge paradigm that we reported for pristine metal oxide NPs. This demonstrates that the surface charge paradigm is a valuable tool to predict the toxicity of NPs.

Lysosome mediates toxicological effects of polyethyleneimine-based cationic carbon dots

“…Furthermore, a comparative study recently demonstrated that CDs prepared from candle soot and subsequently coated with PEI, so they display a net positive charge, were more toxic towards cultured fibroblasts than negatively charged pristine CDs (Havrdova et al 2016). Therefore, as previously reported for silicon- (Shahbazi et al 2013), silver-(El Badawy et al 2011), or polystyrene-based NPs (Kim et al 2016), or for CNTs (Li et al 2013), the surface charge seems to impact on CD safety, a cationic charge being associated with higher toxicological risks. However, the mechanisms involved in the cytotoxicity of cationic CDs remain poorly explored.…”

“…Surface charge is well known for its drastic influence on nanomaterials biocompatibility (El Badawy et al 2011;Kim et al 2016;Li et al 2013;Shahbazi et al 2013). Regarding CDs, some authors reported that cationic CDs prepared from bPEI25k exhibit some cytotoxicity towards cells of various tissue origins (Liu et al 2012;Pierrat et al 2015).…”

The curious case of how mimicking physiological complexity in in vitro models of the human respiratory system influences the inflammatory responses. A preliminary study focused on gold nanoparticles

“…Such inflammatory mechanisms have been thoroughly investigated and elucidated. To date, it is commonly accepted that the NPs physico-chemical properties (such as composition, size, surface charge, and agglomeration) (Braakhuis, Park, Gosens, De Jong, & Cassee, 2014;Kim et al, 2016;Kreyling, Semmler-Behnke, Takenaka, & Moller, 2013;Madl, Plummer, Carosino, & Pinkerton, 2014;Rotoli et al, 2015), as well as the timing (acute vs. chronic) and route (e.g., intratracheal or intranasal) of administration (Landsiedel, Sauer, Ma-Hock, Schnekenburger, & Wiemann, 2014;Morimoto et al, 2016), strongly influence the lung inflammatory response to NPs (Mohamud et al, 2014). Most of these paradigms have been extrapolated from the data originating from animal studies, which are widely used for evaluating inflammatory responses in inhalation toxicology studies.…”

Assessment of the physicochemical properties of chrysotile-containing brake debris pertaining to toxicity

“…As most recently discussed by Gualtieri (2018) in relation to a predictive model of mineral fiber pathogenicity, surface reactivity can play a role in particle/ fiber toxicity. Indeed, attributes such as surface charge have been shown to influence respiratory toxicity of particles such metal oxides (Cho et al 2012) and even polystyrene nanoparticles (Kim et al 2016). In relation to chrysotile, the impact of surface charge on cell injury has been known for some time (Light and Wei 1977) whereby the highly charged surface of chrysotile can cause adverse membrane interactions (as demonstrated by high hemolytic activity).…”