Gram-Scale Preparation of Iron Oxide Nanoparticles with Renal Clearance Properties for Enhanced <i>T</i>₁-Weighted Magnetic Resonance Imaging

Abstract

Extremely small-sized iron oxide nanoparticles (ESIONs) have been accepted as a potential alternative to gadolinium-based contrast agents for enhanced <i>T</i>₁-weighted MR imaging. Recently developed zwitterion-coated ESIONs showed a high <i>T</i>₁ 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 <i>r</i>₁ relaxivity of 2.4 mM^-1 s^-1 and <i>r</i>₂/<i>r</i>₁ ratio as low as 2.2 at 1.0 T guarantee their application as effective <i>T</i>₁ 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 <i>T</i>₁ MRI contrast effect, appropriate circulation time, and renal clearable property would render ZUIONs attractive for practical applications.