Development of a novel polysaccharide-based iron oxide nanoparticle to prevent iron accumulation-related osteoporosis by scavenging reactive oxygen species.

In this work, the biological polysaccharide-based antioxidant polyglucose-sorbitol-carboxymethyl ether (PSC) was used as the precursor to synthesize Fe2O3@PSC nanoparticles, which are expected to scavenge excess reactive oxygen species (ROS) to inhibit osteogenesis and promote osteoclast differentiation in iron accumulation (IA)-related osteoporosis. The Fe2O3@PSC nanoparticles obtained were of a uniform particle size of 7.3 nm with elemental O/Fe/Cl/C at a ratio of 190:7:2:88. In addition, the Fe2O3@PSC nanoparticles showed the ability to supply equivalent amounts of iron as the typical iron agent ferric ammonium citrate (FAC) in vitro and in vivo. Importantly, the Fe2O3@PSC nanoparticles not only induced antioxidative MC3T3-E1 and Raw 264.7 cells to scavenge ROS but also promoted osteogenic differentiation by activating Akt-GSK-3β-β-catenin and inhibiting osteoclast differentiation by inhibiting the MAPK and NF-κB pathways in vitro. In vivo, no IA-related osteoporosis was induced in a mouse model when enough iron was supplied by the Fe2O3@PSC nanoparticles. Overall, the biological polysaccharide-based antioxidant PSC can supply iron and prevent IA-related osteoporosis, indicating that it is a promising novel iron agent for applications to treat iron deficiency diseases.