Rutin‐Coated Ultrasmall Gadolinium Oxide Nanoparticles with High T1 Relaxivity for MRI of Blood Vessels and Glucose Transporter‐Overexpressing Malignant Tumors

ABSTRACT The straightforward one‐step wet‐chemical approach represents a promising strategy for the preparation of ultrasmall gadolinium oxide nanoparticles (GdONs) featuring high T 1 relaxivity and excellent aqueous dispersion stability. However, achieving specificity for conventional GdONs still requires multi‐step modifications with targeting molecules, introducing uncertainty into their application prospects. Herein, rutin (Ru)‐coated ultrasmall GdONs (Gd@Ru) possessing both high T 1 relaxivity and glucose transporter (GLUT)‐overexpressing tumor‐targeted magnetic resonance imaging (MRI) capability were successfully prepared via a one‐step wet‐chemical method. Among all the as‐prepared Gd@Ru, Gd@Ru‐5 with the lowest Gd content (∼3.8 wt% Gd, as determined by EDS) exhibits the smallest crystalline size (∼ 1.8 nm) and hydrodynamic diameter (∼ 4.0 nm), achieving the highest T 1 relaxivity (40.4 mM − 1 s − 1 at 1.5 T) along with exceptional stability. Moreover, Gd@Ru‐5 showed satisfactory biosafety and excellent magnetic resonance angiography (MRA) performance in SD rats and New Zealand rabbits, as well as effective targeted imaging of GLUT‐overexpressing 4T1 breast tumors. Overall, we present a facile one‐step wet‐chemical strategy for fabricating ultrasmall GdONs that integrate high T 1 relaxivity, excellent MRA performance, and tumor‐targeted MRI capability.