A Closed‐Loop Cascade Strategy for On‐Demand Regulation of Uric Acid

Abstract Despite that the current anti‐hyperuricemia drugs can effectively reduce uric acid (UA) levels, imprecise medication dosage or uncontrolled lowering of UA levels may result in undesired effects. To address this issue, a closed‐loop cascade strategy based on a biocompatible network composite, NW‐FPNP/uricase (UOX), is proposed for on‐demand regulation of UA levels. NW‐FPNP/UOX is constructed by encapsulation of UOX) as UA‐responsive element and FPNP, a nanoparticle of phenylboronic acid modified xanthine oxidase (XOD) inhibitor febuxostat, as H 2 O 2 ‐sensitive element with AMP/Gd 3+ network. It interrelates the UA metabolization and generation processes into a closed loop of cascade reactions involving UOX‐catalyzed UA metabolization and H 2 O 2 generation, H 2 O 2 ‐triggered febuxostat regeneration and XOD inhibition, and XOD‐catalyzed UA generation. Through UA level‐dependent auto‐adjustment of XOD activity, specially 6% at 600 × 10 −6 m UA compared to 82% at 100 × 10 −6 m , UA levels can be regulated to an appropriate range through dynamically balancing UA metabolization and generation. This biocompatible on‐demand UA regulation system prevents the overdose of UA‐lowering medications and avoids hypouricemia in hyperuricemia treatment, demonstrating great potential in intelligent UA level management. This work also introduces a new concept of a closed‐loop cascade strategy for on‐demand regulation of biochemical indicators within specific thresholds.