Scale-Up Preparation of Manganese-Iron Prussian Blue Nanozymes as Potent Oral Nanomedicines for Acute Ulcerative Colitis

Prussian blue (PB) nanozymes are demonstrated as effective therapeutics for ulcerative colitis (UC), yet an unmet practical challenge remains in the scalable production of these nanozymes and uncertainty over their efficacy. With a novel approach, a series of porous manganese-iron PB (MnPB) colloids, which are shown to be efficient scavengers for reactive oxygen species (ROS) including hydroxyl radical, superoxide anion, and hydrogen peroxide, are prepared. In vitro cellular experiments confirm the capability of the nanozyme to protect cells from ROS attack. In vivo, the administration of MnPB nanozyme through gavage at a dosage of 10 mg kg-1 per day for three doses in total potently ameliorates the pathological symptoms of acute UC in a murine model, resulting in mitigated inflammatory responses and improved viability rate. Significantly, the nanozyme produced at a large scale can be achieved at an unprecedented yield weighting approximate to 11 g per batch of reaction, demonstrating comparable anti-ROS activities and treatment efficacy to its small-scale counterpart. This work represents the first demonstration of the scale-up preparation of PB analog nanozymes for UC without compromising treatment efficacy, laying the foundation for further testing of these nanozymes on larger animals and promising clinical translation. A novel, green, and straightforward approach is developed to macroscopically produce manganese-iron Prussian blue (PB@MnPB and MnPB) analog nanozymes, yielding approximate to 11 grams of product per batch of reaction. These nanozymes exhibit superior multienzyme-like antioxidation activities, and display effectiveness in the treatment of acute colitis with outstanding biocompatibility. image