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

Abstract

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.

Asymmetric Monolayer Mesoporous Nanosheets of Regularly Arranged Semi-Opened Pores via a Dual-Emulsion-Directed Micelle Assembly

“…Two reasons account for it. The first is that the building units assembled on solid or liquid interfaces lack a strong pulling force in the direction perpendicular to the 2D planes (interfaces). , So, by the conventional methods, the micelle/oligomer composite units can just contract along the plane directions to form a common ring-like mesopore with a symmetrical surface. − Another one is the assembly units of the oligomer/micelle composites mostly are thermodynamically instable in the conventional methods, which can easily cause a phase-transition or induce the serious cross-linking among adjacent micelles. − This reason normally results in an irregular pore configuration and thick multilayered structure. So, it is important to develop a new strategy, which not only can stabilize the micelle units but also offers a strong force to direct the contraction direction of oligomer/composite monomicelle on interfaces.…”