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Superparamagnetic iron oxide nanoparticles (SPIONs, ~11-nm cores) were PEGylated without anchoring groups and studied as efficient MRI  T   2  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 −1 s −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 agentElectronic supplementary material  The online version of this article (doi:10.1186/s11671-017-2084-y) contains supplementary material, which is available to authorized users.

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