Multimodal smart systems reprogramme macrophages and remove urate to treat gouty arthritis

Nat Nanotechnol. 2024 Oct;19(10):1544-1557. doi: 10.1038/s41565-024-01715-0. Epub 2024 Jul 17.

Abstract

Gouty arthritis is a chronic and progressive disease characterized by high urate levels in the joints and by an inflammatory immune microenvironment. Clinical data indicate that urate reduction therapy or anti-inflammatory therapy alone often fails to deliver satisfactory outcomes. Here we have developed a smart biomimetic nanosystem featuring a 'shell' composed of a fusion membrane derived from M2 macrophages and exosomes, which encapsulates liposomes loaded with a combination of uricase, platinum-in-hyaluronan/polydopamine nanozyme and resveratrol. The nanosystem targets inflamed joints and promotes the accumulation of anti-inflammatory macrophages locally, while the uricase and the nanozyme reduce the levels of urate within the joints. Additionally, site-directed near-infrared irradiation provides localized mild thermotherapy through the action of platinum and polydopamine, initiating heat-induced tissue repair. Combined use of these components synergistically enhances overall outcomes, resulting in faster recovery of the damaged joint tissue.

MeSH terms

  • Animals
  • Arthritis, Gouty* / drug therapy
  • Arthritis, Gouty* / metabolism
  • Arthritis, Gouty* / therapy
  • Exosomes / chemistry
  • Exosomes / metabolism
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyperthermia, Induced / methods
  • Indoles / chemistry
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Liposomes / chemistry
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Male
  • Mice
  • Polymers / chemistry
  • Resveratrol / chemistry
  • Resveratrol / pharmacology
  • Urate Oxidase / chemistry
  • Urate Oxidase / pharmacology
  • Uric Acid*

Substances

  • Uric Acid
  • polydopamine
  • Polymers
  • Hyaluronic Acid
  • Urate Oxidase
  • Liposomes
  • Resveratrol
  • Indoles