10.1021/am4045713.s001 Robert A. Roggers Robert A. Roggers Madhura Joglekar Madhura Joglekar Justin S. Valenstein Justin S. Valenstein Brian G. Trewyn Brian G. Trewyn Mimicking Red Blood Cell Lipid Membrane To Enhance the Hemocompatibility of Large-Pore Mesoporous Silica American Chemical Society 2014 MSN Mimicking Red Blood Cell Lipid Membrane hemocompatibility flow cytometry analyses material bilayer composition RBC UV cholesterol 2014-02-12 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Mimicking_Red_Blood_Cell_Lipid_Membrane_To_Enhance_the_Hemocompatibility_of_Large_Pore_Mesoporous_Silica/2323102 Mesoporous silica nanoparticles (MSNs) have been repeatedly demonstrated as potential drug-delivery devices. The study of biocompatibility and interaction of these materials with the various cell types is of great interest with regard to the development of viable pharmaceutical products. By mimicking the cholesterol, phosphatidylcholine, and phosphatidylethanolamine composition of the outer leaflet of a human red blood cell (RBC), lipid-bilayer-coated mesoporous silica particles show considerably improved hemocompatibility over phosphatidylcholine-coated and uncoated large-pore MSN (<i>l</i>-MSN). These inorganic/organic composite nanomaterials are shown to be capable of interfacing with RBCs without damaging the cells even at relatively high concentrations, as observed through electron microscopy, UV–vis spectroscopy, and flow cytometry analyses. Interestingly, the absence of cholesterol in the outer bilayer composition is shown to produce toxic effects without resulting in hemolysis. By maintaining the ζ potential of lipid-bilayer-functionalized MSNs similar to that of the hemolytic <i>l</i>-MSNs, we demonstrate that the bilayer composition, and not the surface charge, plays a significant role in determining the hemocompatibility of MSN-based materials.