Iron oxide/manganese oxide co-loaded hybrid nanogels as pH-responsive magnetic resonance contrast agents

Abstract This work described a proof of concept study of hybrid nanogel-based magnetic resonance contrast agents, SPIO@GCS/acryl/biotin@Mn-gel, abb. as SGM, for highly efficient, pH-responsive T1 and T2 dual-mode magnetic resonance imaging (MRI). SGM have been synthesized by assembling superparamagnetic iron oxide particles into polysaccharide nanoclusters, followed by in-situ reduction of the manganese species on the clusters and a final mild polymerization. The dual-mode SGM showed an interesting pH-responsiveness in in vitro MRI, with both T1 and T2 relaxivities turned “ON” in the acidic environment, along with an increase in the r1 and r2 relaxivity values by 1.7-fold (from 8.9 to 15.3 mM−1 S−1 ) and 4.9-fold (from 45.7 to 226 mM−1 S−1 ), due to desirable silencing and de-silencing effects. This interesting acidic-responsiveness was further verified in vivo with both significantly brightened signal of tumor tissue in T1 -weighted MR images and a darkened signal in T2 -weighted MR images 50 min post-injection of SGM. This smart hybrid nanogel may serve as a promising candidate for further studies of dual-mode (T1 and T2 ) contrast agents in MRI, due to its high stability, interesting pH-response mechanism and indicative imaging of tumors.