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Zeng, R.* ; Lv, B.* ; Lin, Z.* ; Chu, X.* ; Xiong, Y.* ; Knoedler, S. ; Cao, F.* ; Lin, C.* ; Chen, L.* ; Yu, C.* ; Liao, J.M.* ; Zhou, W.* ; Dai, G.* ; Shahbazi, M.A.* ; Mi, B.* ; Liu, G.*

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

Bioact. Mater. 34, 366-380 (2024)

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

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Biomimetic Nanoparticle ; Diabetes ; Macrophage Polarization ; Macrophages Cell Membranes ; Wound Healing; Nedd8-activating Enzyme; Inhibitor

ISSN (print) / ISBN 2452-199X

e-ISSN 2452-199X

Journal Bioactive Materials

Quellenangaben Volume: 34, Pages: 366-380

Publisher KeAi Communications Co.

Publishing Place 16 Donghuangchenggen North St, Building 5, Room 411, Beijing, Dongcheng District 100009, Peoples R China

Non-patent literature Publications

Institute(s) Institute of Regenerative Biology and Medicine (IRBM)

Grants Scientific Research Project in Health System of Pingshan District
Medical Research Foundation of Guangdong Province
Natural Science Foundation of Shenzhen Municipality
Hubei Province Unveiling Science and Technology Projects
Chinese Pharmaceutical Association Hospital Pharmacy department
Department of Science and Technology of Hubei Province
Wuhan Science and Tech-nology Bureau
National Science Foundation of China