Nie Chenyao, Xu Ji, Zhao Yuhui, Nan Ke, Tan Manqi, Liu Zhaobo, Huang Ming, Ren Wenzhi, Wang Bing
School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, 325035, P. R. China.
Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang, 315201, P. R. China.
Adv Healthc Mater. 2025 Jan;14(2):e2403004. doi: 10.1002/adhm.202403004. Epub 2024 Oct 30.
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 HO-sensitive element with AMP/Gd network. It interrelates the UA metabolization and generation processes into a closed loop of cascade reactions involving UOX-catalyzed UA metabolization and HO generation, HO-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 m UA compared to 82% at 100 × 10 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.
尽管目前的抗高尿酸血症药物可以有效降低尿酸（UA）水平，但用药剂量不准确或UA水平控制不当可能会产生不良影响。为了解决这个问题，提出了一种基于生物相容性网络复合材料NW-FPNP/尿酸酶（UOX）的闭环级联策略，用于按需调节UA水平。NW-FPNP/UOX是通过将UOX（作为UA响应元件）和FPNP（一种苯基硼酸修饰的黄嘌呤氧化酶（XOD）抑制剂非布司他的纳米颗粒，作为HO敏感元件）封装在AMP/Gd网络中构建而成。它将UA代谢和生成过程关联到一个级联反应的闭环中，包括UOX催化的UA代谢和HO生成、HO触发的非布司他再生和XOD抑制，以及XOD催化的UA生成。通过XOD活性的UA水平依赖性自动调节，特别是在600×10⁻⁶ m UA时为6%，而在100×10⁻⁶ m时为82%，可以通过动态平衡UA代谢和生成将UA水平调节到适当范围。这种生物相容性按需UA调节系统可防止UA降低药物过量，并避免高尿酸血症治疗中的低尿酸血症，在智能UA水平管理中显示出巨大潜力。这项工作还引入了一种闭环级联策略的新概念，用于在特定阈值内按需调节生化指标。
