Folic Acid-modified Lysozyme-protected Gold Nanoclusters as Anti-inflammatory Nanomedicine for Gout Flares

Abstract

\n BackgroundGout normally occurs when excess urate crystals accumulate in the joints that induce inflammation. The inflammations further result in gout flares, causing serious pain. Some anti-inflammatory drugs can relieve pain, but they have significantly toxic and side effects. Nanomedicines offer opportunities to reduce various side effects but are mostly based on the delivery of additional organic drugs, which adds complexity and may cause other health problems including the bioaccumulation risk. We developed folic acid (FA)-modified lysozyme (Lys)-protected gold nanoclusters (AuNCs) (i. e., FLA) by a one-pot method, and FLA is developed as an anti-inflammatory drug in the treatment of acute attacks of gout flares at high monosodium urate (MSU) levels. MethodsThe morphological changes of the cells caused by FLA were studied by Transmission electron microscopy (TEM) and fluorescence microscopy. Western blotting was conducted to understand the inflammation factors. AutoDock Vina was used for molecular docking of FLA to evaluate the binding mode of the ligand and the interaction in the active site.ResultsThis nanomedicine significantly reduced the inflammation of gout flares. In addition, the oxidative stress level was found to decrease to normal values by FLA based on the evaluation of reactive oxygen species (ROS). By injecting FLA into the gout rat model, inflammation was remarkably reduced during gout attacks, and cartilage destruction was significantly relieved. The biosafety of this nanomedicine is confirmed by insignificant cytotoxicity and no bioaccumulation-induced organ change.ConclusionCompared with traditional nano-delivery systems, this organic drug-free nanomedicine exhibits exciting therapeutic efficiency against gout flares, which will have considerable prospects in the clinic.