Extremely Small Iron Oxide Nanoparticles with pH-Dependent Solubility Transition as T1/T2 Switchable Contrast Agents for MRI

Extremely small iron oxide nanoparticles (ESIONPs), which have a switchable contrast signal and a favorable biocompatibility, are gaining considerable attention as smart magnetic resonance imaging (MRI) contrast agents (CAs). Adaptive MRI CAs could improve the accuracy of tumor diagnosis because they realize rapid imaging signal conversion under an endogenous stimulus. Herein, based on the hydrophilic to hydrophobic transition of polymers, we propose a pH-responsive T 1 /T 2 switchable ESIONP contrast agent. ESIONPs are functionalized at the surface with adamantane groups through a polyethylene glycol (PEG) chain, and subsequently, a stimuli-responsive polymer (PSDM) with pH-dependent solubility is introduced through the host–guest interaction between adamantane and β-cyclodextrin (β-CD). The obtained ESIONPs-PEG-PSDM is equipped with remarkable pH responsiveness, which triggers the aggregation of ESIONPs under the tumor acid condition, leading to the switch from a T 1 to a T 2 contrast agent. In vivo MRI experiments show that the T 2 contrast signal is selectively enhanced at the tumor location after injection of ESIONPs-PEG-PSDM. Therefore, ESIONPs-PEG-PSDM with pH-induced hydrophilic to hydrophobic transition is a potential smart MRI contrast agent for precise tumor diagnosis.