1. Bio-inspired nanoenzyme for metabolic reprogramming and anti-inflammatory treatment of hyperuricemia and gout
- Author
-
Cheng Zhang, Ze-Nan Zhuang, Xian-Zheng Zhang, Chi Zhang, Lu Zhang, Pei Pan, and Chu-Xin Li
- Subjects
musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,0303 health sciences ,Inflammatory arthritis ,medicine.medical_treatment ,nutritional and metabolic diseases ,Inflammation ,02 engineering and technology ,General Chemistry ,Pharmacology ,021001 nanoscience & nanotechnology ,medicine.disease ,Gout ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,Cytokine ,chemistry ,In vivo ,medicine ,Uric acid ,Hyperuricemia ,medicine.symptom ,0210 nano-technology ,030304 developmental biology - Abstract
Gout, a common type of inflammatory arthritis resulting from chronic elevation of uric acid (UA) level, is usually accompanied with hyperuricemia. The current clinical drugs for the treatment of gout and hyperuricemia are greatly restricted by their limited therapeutic efficacy, off-target toxicity and severe side effects. Here, a neutrophil membrane (NM)-coated and cascade catalytic nanoenzyme was devised with excellent inflammation targeting, inflammatory cytokines neutralizing and UA degrading characteristics for the treatment of gout and hyperuricemia with high efficacy and safety. This nanoenzyme was fabricated by encapsulating uricase (UOx) and catalase (CAT) into zeolitic imidazolate framework-8 (ZIF-8) and further coating it with NM. The NM-coated nanoenzyme inherits the antigenic exterior and cell membrane functions of neutrophils for inflammation targeting and cytokine neutralization. UOx and CAT encapsulated in ZIF-8 could efficiently degrade UA and eliminate hydrogen peroxide (H2O2) via a biocatalytic cascade, thus successfully blocking the inflammation amplification during gout development. Both in vitro and in vivo experiments demonstrated the preferable potentials of the nanoenzyme for gout targeting, inflammation elimination and UA degradation, exhibiting great promise for the treatment of gout and hyperuricemia in an effective and safe manner.
- Published
- 2021