Liu Lu, Li Xiurong, Chen Yongxian, Gao Junbin, Jiang Yuejun, Ye Yicheng, Wang Peng, Peng Fei, Tu Yingfeng
Pharmacy Department, The Fifth Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, China.
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Nat Commun. 2025 Mar 8;16(1):2339. doi: 10.1038/s41467-025-56100-9.
Uricase (UOx)-based gout treatments are generally limited due in part to the accumulation of HO in an arthrosis environment characterized by a sluggish metabolism. Here we develop a self-cascade nanomotor with high efficiency toward simultaneous uric acid (UA) degradation and HO elimination on the basis of UOx and sodium citrate loading in amine functionalized hollow mesoporous silica nanoparticles (AHMSNs). Due to the inherent asymmetry of AHMSNs, the developed nanomotors can be actuated by ionic diffusiophoresis induced by the enzymatic UA degradation, thus enlarging the diffusion range within the joint cavity. HO generated during UA decomposition can be simultaneously eliminated by the loaded sodium citrate, resulting in a considerable improvement in mammalian cell viability. In vivo studies display powerful therapeutic effect in gouty models using this self-cascade nanomotor system. These results present the potential of nanomotors as active therapeutic agents for gout, providing a perspective on the application of enzyme-driven micro/nanomotors.
基于尿酸酶(UOx)的痛风治疗方法通常受到限制,部分原因是在代谢缓慢的关节环境中过氧化氢(HO)会积累。在此,我们基于负载于胺功能化中空介孔二氧化硅纳米颗粒(AHMSNs)中的尿酸酶(UOx)和柠檬酸钠,开发了一种自级联纳米马达,其对尿酸(UA)降解和过氧化氢消除具有高效性。由于AHMSNs固有的不对称性,所开发的纳米马达可由酶促尿酸降解诱导的离子扩散电泳驱动,从而扩大关节腔内的扩散范围。尿酸分解过程中产生的过氧化氢可同时被负载的柠檬酸钠消除,从而显著提高哺乳动物细胞活力。体内研究表明,使用这种自级联纳米马达系统在痛风模型中具有强大的治疗效果。这些结果展示了纳米马达作为痛风活性治疗剂的潜力,为酶驱动的微/纳米马达的应用提供了一个视角。