Short Zwitterionic Sulfobetaine-Modified Silica Nanoparticles: Is Neutrality Possible?

Zwitterionic coatings are an efficient strategy for preventing biomolecule adsorption and enhancing nanoparticle stability in solution. The properties of zwitterions and other antifouling materials, including suppression of nonspecific adsorption and improved colloidal stability of nanoparticles, are believed to derive from their electroneutral and highly hydrophilic nature. Among different zwitterions, short sulfobetaines have been demonstrated to be effective in preventing protein adsorption onto several nanoparticles and providing enhanced colloidal stability. Although zwitterionic sulfobetaine silane (ZS) is electrically neutral, the negatively charged zwitterionic sulfobetaine-functionalized silica nanoparticles (ZS@SiO 2 NPs) exhibit a similar ζ-potential to nonfunctionalized silica nanoparticles (SiO 2 NPs). In this work, we present a thorough comprehension of the surface properties of ZS@SiO 2 NPs, which encompasses the development of meticulous functionalization procedures, detailed characterization approaches, and cutting-edge modeling to address the questions that persist regarding the surface features of ZS@SiO 2 NPs. The negative charge of ZS@SiO 2 NPs is due to the stabilization of siloxide from residual surface silanols by the quaternary amine in the sulfobetaine structure. Consequently, we infer that zero-charge ZS@SiO 2 NPs are unlikely to be obtained since this stabilization increases the dissociation degree of surface silanols, increasing the overall structure negative charge. Additionally, colloidal stability was evaluated in different pH and ionic strength conditions, and it was found that ZS@SiO 2 NPs are more stable at higher ionic strengths. This suggests that the interaction between ZS and salt ions prevents the aggregation of ZS@SiO 2 NPs. Together, these results shed light on the nature of the ZS@SiO 2 NP negative charge and possible sources for the remarkable colloidal stability of zwitterionic nanoparticles in complex media.