Multimodal smart systems reprogramme macrophages and remove urate to treat gouty arthritis.
Jingxin XuMingjun WuJie YangDezhang ZhaoDan HeYingju LiuXiong YanYuying LiuDaojun PuQunyou TanLing ZhangJingqing ZhangPublished in: Nature nanotechnology (2024)
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.
Keyphrases
- anti inflammatory
- drug delivery
- rheumatoid arthritis
- stem cells
- mesenchymal stem cells
- oxidative stress
- high glucose
- electronic health record
- diabetic rats
- drug induced
- type diabetes
- radiation therapy
- magnetic nanoparticles
- machine learning
- deep learning
- adipose tissue
- drug release
- radiation induced
- cell therapy
- glycemic control
- weight loss
- insulin resistance