Abstract Superior aqueous dispersibility mitigates nanoparticle toxicity in biological systems while preventing agglomeration. Herein, a hydrogen‐bond‐mediated aqueous synthesis strategy is proposed, utilizing β‐cyclodextrin (β‐CD) and sodium citrate (SC) to directly fabricate metal oxide nanoparticles in a single step. This approach not only suppresses particle aggregation but also preserves the molecular integrity of surface modifiers under high‐temperature reaction conditions. Taking the preparation of gadolinium oxide as an example. Through modifier molecules on Gd 2 O 3 surfaces, the hydrophilicity is markedly enhanced, enabling stable dispersion in aqueous media, which is a critical prerequisite for biomedical applications. This green synthesis method, regulated by hydrogen‐bonding interactions, overcomes safety concerns associated with organic solvents in traditional solvothermal techniques and gadolinium ion leakage in co‐precipitation methods, while eliminating complex post‐modification steps. The longitudinal relaxation rate (r1) of Gd 2 O 3 UPs‐220, prepared by this method, achieves 8.43 m m −1 s −1 at a magnetic field strength of 7.0 T, demonstrating excellent magnetic resonance imaging (MRI) enhancement performance. This synthetic strategy provides an approach for preparing water‐dispersible metal oxides.
Zhang et al. (2025) studied this question.