Shielding and stealth effects of zwitterion moieties in double-functionalized silica nanoparticles

Surface functionalization of silica nanoparticles (SiO2NPs) has been considered as a promising strategy to develop target-specific nanostructures. However, finding a chemical functionalization that can be used as an active targeting moiety while preserving the nanoparticles colloidal stability in biological fluids is still challenging. We present here a dual surface modification strategy for SiO2NPs where a zwitterion (ZW) and a biologically active group (BAG) (amino, mercapto or carboxylic functionalities) are simultaneously grafted on the nanoparticles’ surface. The rationale behind this strategy is to generate colloidally stable nanoparticles and avoid the nonspecific protein adsorption due to ZW groups insertion, while the effective interaction with biosystems is guaranteed by the BAGs presence. The biological efficacy was tested against VERO cells, E. coli bacteria and Zika viruses and a similar trend was observed for all tested particles. The desirable “stealth property” to prevent nonspecific protein adhesion also generated a ZW shielding effect of the BAG functionality hindering their proper interaction and activity in cells, bacteria and viruses553540548CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP440379-2016-4; 130767-201615/25406-5; 16/16905-0; 16/21598-0; 17/01167-7; 17/06692-2;17/09203-2The authors would like to acknowledge the financial support of the São Paulo Research Foundation – FAPESP (processes 15/25406-5, 16/16905-0, 16/21598-0, 17/01167-7, 17/06692-2 and 17/09203-2), CNPq, Capes and Decit (processes 440379-2016-4 and 130767-2016-1). The authors also thank LME and LCS labs in LNNano – CNPEM for the use of electron microscopy and atomic force microcopy facilitie