Acoustofluidic Fabrication of Calcium Pyrophosphate-Enzyme Nanocatalysts for Oral Treatment of Metabolic Disorders

Catalytic medicine, particularly enzyme-based therapies, has emerged as a promising approach for disease treatment. However, the development of enzyme-based catalytic medicines faces significant challenges, including a complex fabrication processes, poor stability, and limited efficacy in oral administration. Herein, we present an approach to fabricate calcium pyrophosphate (CaP)-enzyme nanocatalysts via acoustofluidic synthesis, enabling rapid and scalable encapsulation of natural enzymes (e.g., uricase, alcohol oxidase, and glucose oxidase). This technique achieves an enzyme loading capacity of ∼45%, significantly surpassing traditional methods. The porous architecture of CaP nanoparticles provides extensive reaction channels, preserving the enzymatic kinetics comparable to free enzymes. Lyophilized into a stable powder form, the nanocatalysts exhibit long-term storage stability (t1/2 ∼ 2.5 years) and resistance to degradation in gastrointestinal fluids, addressing the critical limitations of free enzymes in oral delivery. In murine models of alcohol intoxication, hyperuricemia, and diabetes, oral administration of these nanocatalyst capsules results in substantial reductions in uric acid, alcohol, and blood glucose levels, demonstrating their therapeutic potential for metabolic disorder regulation. The acoustofluidic synthesis method establishes a versatile and scalable platform for the development of enzyme-based therapies, offering transformative potential for clinical applications and advancing the field of catalytic medicine.