Systematic insights into silica shell architecture on iron oxide nanoparticles: Effects of core geometry, TEOS: APTES ratio, and loading

• TEOS:APTES ratio dictates silica shell thickness, morphology, and charge. • DOE reveals how core geometry and loading modulate encapsulation outcomes. • Design rules enable tailoring silica-coated IONPs for biomedical applications. Silica-coated iron oxide nanoparticles are widely used in biomedicine, yet the relationships between several reaction parameters like precursor chemistry, core morphology, and particle loading, that govern coating physico-chemical properties, remain poorly defined. Here, we systematically disentangle these factors using a combination of scanning transmission electron microscopy (S(T)EM), surface charge analysis, magnetic saturation characterization ( Ms ), analytical centrifugation (AC), and nanoparticle tracking analysis (NTA). Initial experiments revealed that tetraethyl orthosilicate (TEOS) alone produced fused, irregular shells, whereas co-condensation with (3-Aminopropyl)triethoxysilane (APTES) yielded discrete, rounded shells with tunable thickness, surface charge, and yield. A custom design-of experiments (DOE) study across spherical and cubic cores (5 or 10 mg loadings; TEOS: APTES = 170:15, 140:45, 110:75 µL) established clear structure–property relationships. TEOS-rich conditions generated thin, single-core shells, while intermediate ratios promoted multi-core architectures with moderate thickness. APTES-rich conditions produced thick, amine functionalized shells, and multi-core encapsulation. Particle loading further modulated coating uniformity, with lower mass favoring thicker shells. These results provide guidelines to rationally tune silica-coated IONPs for application-specific needs, especially in biomedicine.