Versatile ligand exchange for aqueous phase transfer of metal oxide nanoparticles produced by thermal decomposition

Thermal decomposition is a powerful and scalable method for producing highly uniform metal oxide nanoparticles (MONPs). However, the hydrophobic ligands vital for controlling nanocrystal growth prevent MONPs' dispersion in aqueous media, limiting their direct use in biomedical applications. Ligand exchange strategies are commonly employed but typically suffer from inefficiency, limited scalability, and reliance on costly or custom-synthesized ligands. This study presents a facile, rapid, and scalable ligand exchange method for MONPs synthesized via thermal decomposition using sodium tripolyphosphate (STPP), a commercially available, biocompatible ligand with strong affinity for multivalent metal cations. This one-step process achieves effective exchange within 30 min at room temperature and is effective on gram-scale batches of nanoparticles capped with oleylamine, oleic acid, or sodium oleate. The resulting water-dispersible nanoparticles display long-term aqueous colloidal stability, strong surface charge, and retention of their intrinsic magnetic properties. The broad versatility of this method is further demonstrated by applying it to doped iron oxide, manganese oxide, and gadolinium oxide nanoparticles, highlighting its potential as a universal solution for biomedical translation. Finally, facile subsequent functionalization of the hydrophilic MONPs with silica and polydopamine shells provides adaptable platforms for imaging, drug delivery, and other bioapplications.