The interactions of cyclic polyamines with tetraethoxysilane in the conditions of the Stöber synthesis of silica nanoparticles were studied and compared to the behavior of a linear polyamine. Granular core-plain shell hybrid particles were obtained whose morphology and size vary with the nature and amount of added ligand. The influence of polyamines on silica condensation could be understood on the basis of a SN(2) reaction involving a pentacoordinated Si complex and depends on the accessibility and nucleophilicity of the ligand. In this case, the polyamine conformation is the key factor determining its ability to activate silica formation. The final size of the hybrid particles was determined by the aggregation of resulting primary nanoparticles that is controlled by electrostatic interactions, and thus depends on the ligand positive charge. These results were compared to biological and biomimetic processes of silica formation where acid-base/electrostatic interactions of silica precursors with linear polyamines have been described.