Extremely Small Iron Oxide Nanoparticles-Encapsulated Nanogels as a Glutathione-Responsive T1 Contrast Agent for Tumor-Targeted Magnetic Resonance Imaging.

Activatable magnetic resonance imaging (MRI) contrast agents that can be selectively stimulated at tumor region are urgently demanded to realize the efficient and accurate diagnosis of cancers. Here, extremely small iron oxide nanoparticles (ESIONPs) modified with citric acid (ESIONPs-CA) are encapsulated in the disulfide-crosslinked poly(carboxybetaine methacrylate) (poly(CBMA)) nanogels, and the cyclo[Arg-Gly-Asp-D-Tyr-Lys] (c(RGD)) ligand is further introduced to obtain ESIONPs-packaged poly(CBMA) nanogels equipped with tumor-targeted c(RGD) (ICNs-RGD). On the basis of the transformation of clustered ESIONPs to dispersed ones induced by the reducing glutathione (GSH), ICNs-RGD can complete the conversion from a T2 contrast agent to a T1 one, realizing the selective activation of T1 contrasting effect. The GSH-dependent MRI signal conversion of ICNs-RGD is feasible in the tumor cell and tissue. Moreover, ICNs-RGD exhibits the obvious targeting specificity and favorable biocompatibility. On the MRI experiments of tumor-bearing mice, benefiting from the stimuli-responsiveness of GSH and targeting specificity, the T1 contrasting effect of tumor tissue can be selectively enhanced after the intravenous injection of ICNs-RGD. Therefore, tumor-targeted ICNs-RGD with switchable MRI signal derived from the activation of GSH is a potential contrast agent for the efficient and precise tumor diagnosis in the clinic.