In Search of the Chemical Basis of the Hemolytic Potential of Silicas

Abstract

The membranolytic activity of silica particles toward red blood cells (RBCs) has been known for a long time and is sometimes associated with silica pathogenicity. However, the molecular mechanism and the reasons why hemolysis differs according to the silica form are still obscure. A panel of 15 crystalline (pure and commercial) and amorphous (pyrogenic, precipitated from aqueous solutions, vitreous) silica samples differing in size, origin, morphology, and surface chemical composition were selected and specifically prepared. Silica particles were grouped into six groups to compare their potential in disrupting RBC membranes so that one single property differed in each group, while other features were constant. Free radical production and crystallinity were not strict determinants of hemolytic activity. Particle curvature and morphology modulated the hemolytic effect, but silanols and siloxane bridges at the surface were the main actors. Hemolysis was unrelated to the overall concentration of silanols as fully rehydrated surfaces (such as those obtained from aqueous solution) were inert, and one pyrogenic silica also lost its membranolytic potential upon progressive dehydration. Overall results are consistent with a model whereby hemolysis is determined by a defined surface distribution of dissociated/undissociated silanols and siloxane groups strongly interacting with specific epitopes on the RBC membrane.

Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines

“…In contrast, lipid/proteinbased corona formed around the SiNPs in plasma can protect cells from hemolysis (Shi et al, 2012), but will likely not be protective once the complex becomes internalized and processed by the cells. Silanol-associated hydroxyl concentration/density on the surface of pristine SiNPs was shown by others to be associated with their cytotoxic, inflammatory and hemolytic potential (Pavan et al, 2013;Pavan et al, 2014;Zhang et al, 2012). Specifically, strained three-membered silanol groups on fumed amorphous silica surfaces showed the highest potential for cytotoxicity and hemolysis (Zhang et al, 2012).…”

The α–β phase transition in volcanic cristobalite

“…However, if a small proportion of nearly amorphous hydrous silica is responsible for the anomalous DSC endotherm, this may have ramifications for toxicity as the bioreactivity will differ between cristobalite and other arrangements of SiO 2 (e.g. Pavan et al, 2013).…”

Effects of magnetic cobalt ferrite nanoparticles on biological and artificial lipid membranes

“…32,33 It is known that adsorption of NPs onto the surface of RBCs can change cell morphology and erythrocyte sedimentation rate, agglutination of RBCs, and hemolysis. 1,18,27,[34][35][36][37][38][39] An interesting question is whether mechanisms revealed by experimental studies of artificial membranes or computer simulations of interactions between NPs and artificial lipid membranes can also explain the interactions of NPs with biological membranes.…”