Gram-Scale Preparation of Iron Oxide Nanoparticles with Renal Clearance Properties for Enhanced T1-Weighted Magnetic Resonance Imaging

Extremely small-sized iron oxide nanoparticles (ESIONs) have been accepted as a potential alternative to gadolinium-based contrast agents for enhanced T1-weighted MR imaging. Recently developed zwitterion-coated ESIONs showed a high T1 contrast power and efficient renal clearing ability, but the tedious preparation steps that required high-cost, unfriendly experimental conditions and a sophisticated phase transition process would likely hinder their clinical translation. Herein, we present a one-pot gram-scale synthesis of zwitterion-capped ultrasmall iron oxide nanoparticles (ZUIONs). The nanoparticles have a core size as small as 3.7 nm and display high colloidal stability in various buffers. The r1 relaxivity of 2.4 mM–1 s–1 and r2/r1 ratio as low as 2.2 at 1.0 T guarantee their application as effective T1 MRI contrast agents. In vivo studies showed that ZUIONs could induce a significant contrast enhancement in blood pool and be eliminated from the body mainly through the renal excretion pathway. The combined advantageous features including facile preparation, excellent biocompatibility, strong T1 MRI contrast effect, appropriate circulation time, and renal clearable property would render ZUIONs attractive for practical applications.