Chemical exchange saturation transfer MRI-trackable peptide hydrogel for drug release monitoring and targeted therapy in inflammatory bowel disease
Fenfen Li, Ronghua Zhao, Weiping Ding, Jinying Yang, Qingqing Wen, Weiqiang Dou, Lin Chen, Jia Zhang, Bensheng Qiu, Jeff W. M. Bulte, Yue Yuan
Abstract
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.