Toxicity of orally administrated biodegradable mesoporous silica nanoparticles in mice

Organic-inorganic hybrid mesoporous silica nanoparticles (MSNs) have emerged as promising platforms in biomedicine owing to their architecturally sophisticated frameworks, stimulus-responsive properties, and tunable functionalities. Despite their potential, the influence of framework composition on the in vivo fate of MSNs remains insufficiently characterized. Here, we systematically evaluate the toxicity, biodistribution, and immunological impact of MSNs featuring three distinct frameworks-pure Si-O, disulfide-bridged, and diselenide-bridged matrices-following oral administration in mice. None of the MSN variants induced mortality at doses up to 2000 mg/kg. Comprehensive hematological, biochemical, and histopathological analyses revealed no overt toxicity upon repeated exposure. Notably, diselenide-bridged MSNs, characterized by enhanced degradability, exhibited accelerated clearance from the liver, spleen, and kidneys relative to their counterparts. Furthermore, all MSN types demonstrated a high degree of immunological safety, as evidenced by unaltered immune cell profiles and the absence of significant inflammatory responses. These findings provide mechanistic insights into the design of organic-inorganic hybrid MSNs with controllable degradability and clearance kinetics, informing their rational development for biomedical applications.