Impacts of Mesoporous Silica Nanoparticle Size, Pore Ordering, and Pore Integrity on Hemolytic Activity

Abstract

This paper uses the measure of hemolysis to evaluate the toxicity of nonporous and porous silica nanoparticles with varied sizes and investigates the effects of porous structure and integrity on the nanoparticle-cell interaction. The results show that both nonporous and porous silica cause red blood cell membrane damage in a concentration- and size-dependent manner. In the case of mesoporous silica nanoparticles, the size-dependent hemolysis effect is only present when the nanoparticles have long-range ordered porous structure, revealing that pore structure is critical in cell-nanoparticle interactions. Mesoporous silica nanoparticles show lower hemolytic activity than their nonporous counterparts of similar size, likely due to fewer silanol groups on the cell-contactable surface of the porous silica nanoparticles. The extent of hemolysis by mesoporous silica nanoparticles increases as the pore structure is compromised by mild aging in phosphate-buffered solutions, initiating mesopore collapse. The pore integrity of mesoporous silica nanoparticles is examined by TEM, XRD, N(2) adsorption-desorption isotherms, and quantification of dissolved silica. In these nanoparticles, pore stability is clearly an important factor in determining the hemolytic activity; further work demonstrates that nanoparticle-induced hemolysis can be eliminated by modifying the silanol surface with a poly(ethylene glycol) coating.

Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

“…After a 2 h incubation at room temperature, the samples were spun down for the detection of hemoglobin released from hemolyzed RBCs. Surprisingly, contrary to the recently reported trend regarding size, 31 MSNs with larger particle size exhibited a higher hemolytic activity than the small particles ( Figure 2). The hemolytic activity of l-MSNs was first observed at 50 μg mL -1 with 5% hemolysis detected, while a good hemocompatibility (<2% hemolysis) of s-MSN was confirmed at concentrations as high as 100 μg mL -1 .…”

“…The hemolytic activity of l-MSNs was first observed at 50 μg mL -1 with 5% hemolysis detected, while a good hemocompatibility (<2% hemolysis) of s-MSN was confirmed at concentrations as high as 100 μg mL -1 . While a larger particle size may be preferable for hemocompatible MSNs below 225 nm, 31 increasing particle size of MSNs beyond this range will not necessarily improve the hemocompatibility as one might intuitively expect. In addition to particle size, other factors such as the surface area are also expected to affect the hemolytic potential of MSNs.…”

Thermally Activated Delayed Fluorescence Organic Dots (TADF Odots) for Time‐Resolved and Confocal Fluorescence Imaging in Living Cells and In Vivo

“…Since CPy‐Odot shows the potential as the bright angiography agent, it is necessary to evaluate the hemolytic behaviors of CPy‐Odots on Zebrafish red blood cells (RBCs) 35. RBCs were isolated from the whole blood by centrifugation and purified by five times washing with physiological saline.…”

Suppression of the hemolytic effect of mesoporous silica nanoparticles after protein corona interaction: independence of the surface microchemical environment

“…Firstly, it was observed that silanol groups on mesoporous silica structures induce less hemolytic effect compared to rigid spherical nanoparticles possibly due to shape-induced effects, which determine the spatial availability of silanols on the nanoparticle-cell interface. 13 Further, it was observed that: (i) smaller Stöber silica nanoparticles (24 nm) induce a pronounced hemolytic effect when compared with bigger ones (263 nm); 14 (ii) nanostructures with high aspect ratio (nanorods) are more cytotoxic than spherical nanoparticles; 15 (iii) mesoporous silica nanostructures (MSNs) with ordered pores (MCM-41) induce a stronger hemolytic effect compared with non-ordered; 14 (iv) small mesoporous nanoparticles (20 nm) consisted of ethenylenebridged silsesquioxane present very low toxicity 16 and (v) polymers such as PEG (polyethylene glycol) can be used to coat particles in order to greatly reduce the hemolysis. 17 Furthermore, an extensive assessment of the interaction of bare and functionalized porous silica nanomaterials with RBCs concluded that SBA-15-type MSNs cause the deformation of RBCs and consequently lead to their disruption.…”