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 (H2O2) to produce O2, 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, O2 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. CONCLUSIONS: 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.
Subject(s)
Gout , Indoles , Polymers , Reactive Oxygen Species , Uric Acid , Gout/drug therapy , Gout/metabolism , Gout/therapy , Reactive Oxygen Species/metabolism , Animals , Mice , Polymers/chemistry , Indoles/chemistry , Indoles/pharmacology , Nanoparticles/chemistry , Platinum/chemistry , Platinum/pharmacology , Platinum/therapeutic use , Humans , Hydrogen Peroxide/metabolism , Hyperthermia, Induced/methods , RAW 264.7 Cells , Photothermal Therapy/methods , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , MaleABSTRACT
Xiuyan, Liaoning was an important locality of jade material of the Red Mountain Culture in the Neolithic Age in Chinese history where there are two types of raw material of nephrite jades, namely gravel nephrite jade (Hemo Yu in Chinese) and old nephrite jade (Lao Yu in Chinese). In the present paper, Laser Raman spectrum technique was applied to analyze the graphite enclaves in the nephrite jades of the two types of materials. The results show that the graphite enclaves in the two types of jades have different characteristics of Raman spectra, indicating that they probably were formed under different geological conditions, or originated from different ore-forming periods or were exploited from different section of ore body. Hence, laser Raman spectrum technique could be used as a supplementary measure for nondestructive detection to determine the occurrence of jades.