Mn3O4 Nanozyme Loaded Thermosensitive PDLLA-PEG-PDLLA Hydrogels for the Treatment of Inflammatory Bowel Disease

When reactive oxygen species (ROS) accumulate in the body, they can lead to inflammatory bowel disease (IBD) through their oxidative damages to DNA, proteins, and lipids. In this study, a thermosensitive hydrogel-based nanozyme was developed to treat IBD. We first synthesized a manganese oxide (Mn₃O₄) nanozyme with multienzyme activity followed by physically loading with a thermosensitive hydrogel poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide)-based triblock copolymer (PDLLA-PEG-PDLLA). Then, a mouse model based on the inducement of dextran sulfate sodium (DSS) was built to assess the ROS targeting, scavenging, as well as anti-inflammatory ability of Mn₃O₄ nanozymes-loaded PDLLA-PEG-PDLLA (MLPPP). Because of the sharp gelation behavior of PDLLA-PEG-PDLLA in body temperature, the MLPPP nanozyme can easily target the inflamed colon after colorectal administration. Following the formation of a physical protection barrier and sustained release of manganese oxide nanozymes that had diverse enzymatic activities and can effectively scavenge ROS, the administration of the MLPPP nanozyme had a high efficacy for treating colitis mice; importantly, after the treatment with this novel nanoformulation, the levels of the pathological indicators in colons as well as in sera of colitis mice were even comparable to healthy mice. Therefore, the MLPPP nanozyme has a potential application for nanotherapy of IBD and would have great clinical translation prospects.