Hollow ellipsoidal and mesoporous spherical silica nanocarriers for targeted delivery in neurodegenerative disease

Silica-based nanocarriers are highly effective for drug delivery due to their tunable pore sizes, well-defined structures (e.g., mesoporous and hollow), and chemical stability across various physiological and chemical environments. Despite these benefits, their safety profile remains poorly defined, with conflicting findings across healthy and diseased biological models, underscoring the need for more focused and systematic research data. In this study, hollow ellipsoidal (TEM: 204 ± 4 nm, hydrodynamic diameter 251.2 ± 16 nm, zeta potential -21.2 ± 1.9 mV) and mesoporous spherical (TEM: 110 ± 2.4 nm, hydrodynamic diameter 171.3 ± 5 nm, zeta potential -43.4 ± 1.7 mV) silica nanocarriers were synthesized based on the hydrothermal decomposition (180-200 °C) approach and soft and hard template-assisted synthesis etching routes. Their dispersions exhibited excellent control over morphology, mesoporosity, and colloidal stability (the PDI values were below 0.3 (typically 0.1-0.3) under physiological conditions). To evaluate how these structural differences influence biological behavior, the physiological interaction of both silica nanocarriers was assessed in healthy and neuroinflammatory mouse models following intravenous (IV) administration. Behavioral and ATP studies revealed shape-dependent biocompatibility with silica carriers, causing a mild recognition-memory decline in healthy mice but not in the LPS-induced neuroinflammation model. Our dataset emphasizes the importance of particle morphology and surface charge in ensuring the biocompatibility of silica nanocarriers for brain delivery.