Enhanced MRI T 2 Relaxivity in Contrast-Probed Anchor-Free PEGylated Iron Oxide Nanoparticles

Abstract

Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs, ~11-nm cores) were PEGylated without anchoring groups and studied as efficient MRI T2 contrast agents (CAs). The ether group of PEG is efficiently and directly linked to the positively charged surface of SPIONs, and mediated through a dipole-cation covalent interaction. Anchor-free PEG-SPIONs exhibit a spin-spin relaxivity of 123 ± 6 mM−1s−1, which is higher than those of PEG-SPIONs anchored with intermediate biomolecules, iron oxide nanoworms, or Feridex. They do not induce a toxic response for Fe concentrations below 2.5 mM, as tested on four different cell lines with and without an external magnetic field. Magnetic resonance phantom imaging studies show that anchor-free PEG-SPIONs produce a significant contrast in the range of 0.1–0.4 [Fe] mM. Our findings reveal that the PEG molecules attached to the cores immobilize water molecules in large regions of ~85 nm, which would lead to blood half-life of a few tens of minutes. This piece of research represents a step forward in the development of next-generation CAs for nascent-stage cancer detection. Graphical Abstract: Contrast-probed anchor-free PEGylated iron oxide contrast agent[Figure not available: see fulltext.].