Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy

作者：Pei Zhao, Hua-Zhong Hu, Xiaotong Chen, Qi-Yun Jiang, Xue-Zhao Yu, Xiaolin Cen, Shi-Qing Lin, Suiqing Mai, Wei‐Lin Pang, Jinxiang Chen, Qun Zhang · 发表于：Journal of Nanobiotechnology · 年份：2024 · DOI：10.1186/s12951-024-02539-9 · 被引用次数：26 · 研究领域：Gout, Hyperuricemia, Uric Acid、Inflammasome and immune disorders、Thyroid Disorders and Treatments

Abstract Background Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. Results In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H 2 O 2 ) to produce O 2 , which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine’s capacity for UA degradation, O 2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approac...