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Deprotonated silanol groups, also known as silanolates, are negatively charged chemical species (Si-O-) present on the surface and within the mesoporous framework of silica-based nanomaterials (Vallet-Regí et al., 2001, Chemistry of Materials). These groups arise from the loss of a proton from surface silanol (Si-OH) groups, with their abundance determined by the surrounding pH and the material's specific pKa values, which typically fall into two populations around pH 2-4 and 8.5-9 (Ong et al., 1992, Chemical Physics Letters). In nanomedicine, they serve as essential sites for the electrostatic loading of cationic drugs, such as doxorubicin, and influence the release kinetics of these therapeutics (Slowing et al., 2008, Advanced Drug Delivery Reviews). Beyond drug loading, the density of these deprotonated groups dictates the nanoparticle's zeta potential, which in turn affects its colloidal stability and interaction with biological fluids. They play a significant role in the formation of the protein corona, which can mask or enhance the nanoparticle's biological identity (Tenzer et al., 2013, Nature Nanotechnology). Furthermore, the interaction between these anionic groups and the quaternary ammonium cations in cell membrane phospholipids can lead to membrane deformation or lysis (Slowing et al., 2009, Advanced Drug Delivery Reviews). This interaction is a key factor in the hemolytic activity observed with certain silica nanoparticles (Lin and Haynes, 2010, J. Am. Chem. Soc.). Consequently, surface modification or 'capping' of these groups is a common strategy to improve the safety profile of silica-based delivery systems.
Deprotonated silanol groups facilitate the loading of cationic therapeutic agents through electrostatic interactions and hydrogen bonding (Manzano and Vallet-Regí, 2020, Chemical Communications). In a biological context, they can interact with phospholipid headgroups of cell membranes, potentially leading to membrane disruption or endosomal escape via the 'proton sponge' effect (Slowing et al., 2009, Advanced Drug Delivery Reviews).
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