Mesoporous silica nanoparticles for reducing hemolytic activity towards mammalian red blood cells.

Recent reports on the design of silica-based nanomaterials, such as sol–gel, colloidal, and mesoporous silica nanoparticles (MSNs), have shown promising potential in utilizing these materials for controlled release, drug delivery, and other biotechnological applications. Several studies have demonstrated that the biocompatibility of these silica nanoparticles with a variety of cell types in vitro is fairly high. However, the low in vitro cytotoxicity offers no guarantee on the desired high biocompatibility in vivo. In fact, silica materials with amorphous particle morphology are known to cause the hemolysis of mammalian red blood cells (RBCs). This kind of hemolytic behavior raised serious bio-safety concerns regarding the application of amorphous silica for drug delivery involving intravenous administration and transport. Various explanations for the hemolytic effect have been proposed, including the generation of reactive oxygen species induced by the surface of silica, denaturation of membrane proteins through electrostatic interactions with silicate, and the high affinity of silicate for binding with the tetra-alkyl ammonium groups that are abundant in the membranes of RBCs. While the exact mechanism is still under investigation, most researchers agree that the hemolytic activity of silica is related to surface silanol groups. For example, a recent study by Murashov et al. demonstrated that the hemolytic activity of amorphous silica is proportional to the concentration of surface silanol groups of these solid materials. Given the fact that most, if not all, of the aforementioned silica nanoparticles with defined shapes and sizes also have abundant silanols on their surfaces, it is important to investigate the hemolytic properties of these materials with RBCs for potential intravenous applications. Herein, we describe an investigation of the hemolytic properties of a previously reported MSN material with mammalian