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Silica nanoparticles are versatile materials whose physicochemical surface properties can be precisely adjusted. Because it is possible to combine several functionalities in a single carrier, silica-based materials are excellent candidates for biomedical applications. However, the functionality of the nanoparticles can get lost upon exposure to biological media due to uncontrolled biomolecule adsorption. Therefore, it is important to develop strategies that reduce non-specific protein-particle interactions without losing the introduced surface functionality. Herein, organosilane chemistry is employed to produce magnetic silica nanoparticles bearing differing amounts of amino and alkene functional groups on their surface as orthogonally addressable chemical functionalities. Simultaneously, a short-chain zwitterion is added to decrease the non-specific adsorption of biomolecules on the nanoparticles surface. The multifunctional particles display reduced protein adsorption after incubation in undiluted fetal bovine serum as well as in single protein solutions (serum albumin and lysozyme). Besides, the particles retain their capacity to selectively react with biomolecules. Thus, they can be covalently bio-functionalized with an antibody by means of orthogonal click reactions. These features make the described multifunctional silica nanoparticles a promising system for the study of surface interactions with biomolecules, targeting, and bio-sensing.

Multifunctional clickable and protein-repellent magnetic silica nanoparticles