Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Office of Clinical Trial of Drug, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510663, Guangdong, 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, 510515, Guangdong, China.
J Nanobiotechnology. 2024 May 22;22(1):275. 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 (HO) 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.
急性痛风是由于体内各部位单钠尿酸盐（MSU）晶体过度积累，导致局部微环境恶化所致。这种降解的标志是尿酸（UA）水平升高、活性氧（ROS）产生增加、缺氧条件、促炎介质的激增和线粒体功能障碍。
在这项研究中，我们开发了一种多功能纳米粒子聚多巴胺-铂（PDA@Pt），通过利用温和的热疗来协同增强 UA 降解和抗炎作用来治疗急性痛风。在这里，PDA 作为一个基础模板，促进 Pt 壳在纳米球表面上的生长，从而形成 PDA@Pt 纳米药物。在这种治疗剂中，Pt 纳米颗粒催化 UA 的分解，并积极分解内源性过氧化氢（HO）产生 O，有助于缓解缺氧条件。同时，PDA 成分具有非凡的 ROS 清除能力。最重要的是，PDA 和 Pt 壳都在近红外二区（NIR-II）有吸收，这不仅使 PDA@Pt 具有优异的光热转换效率，用于有效的光热治疗（PTT），而且还大大增强了纳米药物对 UA 降解、O 产生和 ROS 清除酶活性的能力。这种光热增强的方法有效地促进了线粒体损伤的修复，并下调 NF-κB 信号通路，抑制促炎细胞因子的表达。
多功能纳米药物 PDA@Pt 在降低 UA 和抗炎作用方面表现出优异的疗效，为急性痛风的治疗提供了一种有前途的潜在治疗策略。
