Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds

• DOI: 10.1016/j.bioactmat.2023.12.025
• Publication Date: 2024-01-06T17:10:28Z
• Authors: Ruiyin Zeng; Bin Lv; Ze Lin; Xiangyu Chu; Yuan Xiong; Samuel Knoedler; Faqi Cao; Chuanlu Lin; Lang Chen; Chenyan Yu; Jiewen Liao; Wu Zhou; Guandong Dai; Mohammad-Ali Shah...; Bobin Mi; Guohui Liu
• Keywords: Proinflammatory cytokine; Macrophage polarization; Mononuclear phagocyte system

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, discovery neddylation, a new type post-translational modification, has been found to regulate various crucial biological processes including cell metabolism cycle. Nevertheless, its capacity control healing wounds diabetic remains unknown. This study shows that MLN49224, compound inhibits neddylation at low concentrations, enhances inhibiting polarization M1 macrophages reducing secretion inflammatory factors. Moreover, it concurrently stimulates growth, movement, formation blood vessel endothelial cells, leading expedited individuals diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). membrane shields from being eliminated reticuloendothelial system counteracts proinflammatory cytokines alleviate inflammation surrounding area. extended discharge MLN4924 M-NPs/MLN4924 growth cells tubes, along towards anti-inflammatory M2 phenotype. By loading hydrogel, final formulation able meaningfully wound, suggesting promising engineered nanoplatform tissue engineering.