Redox-triggered aggregation of ESIONPs with switchable T1 to T2 contrast effect for T2-weighted magnetic resonance imaging

Abstract

Magnetic resonance imaging (MRI) contrast agents (CAs) have drawn increasing attention in cancer diagnosis. However, since the signals they generate are always “on” and may bring interfering background signals to the region of interest, their selectivity and sensitivity need further improvement. Herein, extremely small iron oxide nanoparticles (ESIONPs) conjugated through a disulfide bond with polyethylene glycol (PEG) that is terminally modified with folic acid (FA), namely ESIONPs-s-s-PEG-FA, were designed and synthesized to target tumor tissues and selectively activate the T₂ MRI contrast effect in the reducing environment of tumor cells. Due to the breakage of disulfide bonds by the high glutathione (GSH) concentration in tumor cells, the hydrophilic PEG chains detached from the surface of ESIONPs, which led to the aggregation of ESIONPs and the activation of the T₂ contrast effect. In vitro results showed that ESIONPs-s-s-PEG-FA could effectively target tumors to assemble in the reductive environment and switch from a T₁ contrast agent (CA) to a T₂ one. Furthermore, MRI in tumor-bearing mice also indicated the obvious targeting capacity and the “turn on” of the T₂ contrast effect. In addition, the results of the biosafety assay suggest that the tumor-targeted T₁/T₂ switchable CA is equipped with favorable biocompatibility for cancer diagnosis.