SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) represent a suitable system for several applications especially in nanomedicine. Great efforts have been made to design stable and biocompatible functionalized SPIONs suitable for diagnostics and drug delivery. In particular, zwitterionic-surfactant functionalized SPIONs, obtained through a coating strategy based on hydrophobic interaction, are promising systems for biomedical applications. The size of functionalized SPIONs has emerged as a crucial parameter determining their fate in living organisms. However, not all the proposed functionalization strategies lead to monodispersed systems and SPION clustering often occurs. In this study, we report a systematic investigation on different surfactant-functionalized SPIONs in order to explore the possibility of tuning the particle size by choosing an appropriate amphiphilic molecule. By combining Small-Angle Neutron Scattering (SANS) and Dynamic Light Scattering (DLS) analysis, we have provided a detailed description of the functionalized SPION structure. Furthermore, we have also related the surfactant aggregation properties, i.e. the Critical Micelle Concentration (CMC), to their efficiency in coating the SPION surface. A lack in the formation of a compact shell leads to a clusters formation. On this basis, the present study contributes to furnishing decisive information to define synthetic strategies able to tune functionalized-SPION design.
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