Chemical exchange saturation transfer MRI-trackable peptide hydrogel for drug release monitoring and targeted therapy in inflammatory bowel disease

Hydrogel formulations hold promise for efficient drug delivery in inflammatory bowel disease (IBD) treatment. Non-invasive in vivo spatiotemporal profiling of drug release is highly warranted but clinically difficult due to the need of additional labeling. We have developed an inflammation-targeting olsalazine-conjugated peptide hydrogel (Olsa-Hydrogel) that serves as an exchange saturation transfer magnetic resonance imaging (CEST MRI) activatable prodrug system. Upon conversion of the prodrug Olsa to mesalazine (Mesa), a strong MesaCEST signal could be observed at 8.5 ppm offset from water using a 3.0 T clinical scanner. Rectal administration of Olsa-Hydrogel to inflamed colonic mucosa in a mouse model of IBD led to activation of the MesaCEST signal upon enzymatic release of Mesa, enabling real-time visualization of the drug release process. This was accompanied by a significant improvement in pathophysiological symptoms. The CEST MRI-activatable peptide hydrogel offers a promising strategy for developing targeted drug delivery systems in disease-specific theranostics.