Emerging therapeutic strategies for hyperuricemia: a comprehensive review of nanozymes, biomimetic delivery, gut-targeted systems, and alternative interventions

Hyperuricemia (HUA) is a metabolic disorder with rising global prevalence, closely associated with gouty arthritis, cardiovascular disease, and renal dysfunction. Uric acid contributes to systemic inflammation and oxidative stress through activation of the NLRP3 inflammasome, NF-κB, and MAPK signaling cascades. Existing therapeutic strategies carry substantial limitations: xanthine oxidase inhibitors and uricosuric agents are constrained by adverse effects and suboptimal efficacy, while uricase biologics are hindered by short half-life, high immunogenicity, and toxicity of the catalytic byproduct H₂O₂. To address these challenges, this review applies a problem-level analytical framework that organizes current innovative therapeutic strategies into four progressive dimensions. At the enzyme level, nanozyme-based cascade catalytic systems provide a promising strategy to mitigate catalytic byproduct toxicity and improve uricase stability. At the delivery system level, biomimetic platforms enable coordinated improvements in targeted delivery and immunomodulation. At the gut-targeting level, oral gut-targeted systems shift the therapeutic focus from systemic circulation to the intestinal compartment. At the level of alternative strategies, natural products, mRNA gene therapy, and immune tolerance induction provide complementary therapeutic avenues through multi-target metabolic regulation, restoration of uric acid-degrading capacity, and mitigation of immunological barriers to sustained biologic use. This framework highlights the internal logic connecting these diverse approaches and offers a new perspective for the systematic understanding of emerging therapeutic strategies for hyperuricemia.