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

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; p. 275
• Main Authors: Zhao, Pei, Hu, Hua-Zhong, Chen, Xiao-Tong, Jiang, Qi-Yun, Yu, Xue-Zhao, Cen, Xiao-Lin, Lin, Shi-Qing, Mai, Sui-Qing, Pang, Wei-Lin, Chen, Jin-Xiang, Zhang, Qun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.05.2024; BioMed Central; BMC
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-inflammatory effects; Biodegradation; Biopolymers; Care and treatment; Chemical properties; Gout; Gout - drug therapy; Gout - metabolism; Gout - therapy; Gouty microenvironment; Health aspects; Humans; Hydrogen Peroxide - metabolism; Hyperthermia, Induced - methods; Indoles - chemistry; Indoles - pharmacology; Male; Mice; Nanomedicine; Nanoparticles - chemistry; Photothermal therapy; Photothermal Therapy - methods; Platinum; Platinum - chemistry; Platinum - pharmacology; Platinum - therapeutic use; Polymers - chemistry; RAW 264.7 Cells; Reactive oxygen species; Reactive oxygen species (ROS) scavenging; Reactive Oxygen Species - metabolism; Therapeutics, Experimental; Thermotherapy; Uric Acid; Uric acid degradation; China; Photothermal therapy; Reactive oxygen species (ROS) scavenging; Anti-inflammatory effects; Uric acid degradation; Gouty microenvironment
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02539-9

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. 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 O ) to produce O , 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 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.