Biological responses to core-shell-structured Fe 3 O 4 @SiO 2 -NH 2 nanoparticles in rats by a nuclear magnetic resonance-based metabonomic strategy

Core-shell-structured nanoparticles (NPs) have attracted much scientific attention due to their promising potential in biomedical fields in recent years. However, their underlying mechanisms of action and potential adverse effects following administration remain unknown. In the present study, a H nuclear magnetic resonance-based metabonomic strategy was applied to investigate the metabolic consequences in rats following the intravenous administration of parent NPs of core-shell-structured nanoparticles, Fe O @SiO -NH (Fe@Si) NPs. Alterations reflected in plasma and urinary metabonomes indicated that Fe@Si NPs induced metabolic perturbation in choline, ketone-body, and amino-acid metabolism besides the common metabolic disorders in tricarboxylic acid cycle, lipids, and glycogen metabolism often induced by the exogenous agents. Additionally, intestinal flora metabolism and the urea cycle were also influenced by Fe@Si NP exposure. Time-dependent biological effects revealed obvious metabolic regression, dose-dependent biological effects implied different biochemical mechanisms between low- and high-dose Fe@Si NPs, and size-dependent biological effects provided potential windows for size optimization. Nuclear magnetic resonance-based metabonomic analysis helps in understanding the biological mechanisms of Fe@Si NPs, provides an identifiable ground for the selection of view windows, and further serves the clinical translation of Fe@Si NP-derived and -modified bioprobes or bioagents.