Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS
Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (<i>i.e.</i>, from-M1-to-M2 repolarization). In a murine periodontitis model, locally administered Q@MPDA reduced the presence of inflammatory macrophages, and decreased the levels of inflammatory cytokines (IL-1<i>β</i> and TNF-<i>α</i>) and reactive oxygen species (ROS) in the periodontium. Consequently, it alleviated periodontitis symptoms, reduced alveolar bone loss, and promoted tissue repair. Furthermore, our study revealed that Q@MPDA could inhibit the glycolysis of inflammatory macrophages while enhancing oxidative phosphorylation (OXPHOS), facilitating the shift from M1 to M2 macrophage subtype. Our findings suggest that Q@MPDA is a promising treatment for periodontitis <i>via</i> immunometabolic rewiring.
Authors
- Yongzhuo Huang (ORCID: https://orcid.org/0000-0001-7067-8915)
- Xinxin Ding (ORCID: https://orcid.org/0000-0002-3448-9444)
- Hongchang Lai
- Junyu Shi (ORCID: https://orcid.org/0000-0002-8241-2572)
- Xue Jiang (ORCID: https://orcid.org/0000-0003-2109-8660)
- Jianxu Wei
- Xiaomeng Zhang (ORCID: https://orcid.org/0000-0002-3989-2734)
- Yi Zhang (ORCID: https://orcid.org/0000-0002-6891-9262)
- Yijie Yang (ORCID: https://orcid.org/0000-0002-1434-1012)
- Jie Zhu
Institutions
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Shanghai Ninth People's Hospital (CN)
- Shanghai Institute of Materia Medica (CN)
- National Clinical Research (US)
Publication Details
- Journal
- Acta Pharmaceutica Sinica B
- Published
- 2024-08-12
- DOI
- https://doi.org/10.1016/j.apsb.2024.07.008
- Citations
- 32
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 5.55
Funders
- Taiwan Biobank
- Duchenne Research Fund
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Guangdong Science and Technology Department
- General Hospital of People’s Liberation Army
- Water Resources Department of Guangdong Province
- National Natural Science Foundation of China-Shenzhen Robotics Research Center Project
- Medical Science and Technology Development Foundation, Nanjing Municipality Health Bureau
- National Key Research and Development Program of China
- Shenzhen Fundamental Research and Discipline Layout project
- Startup Project for High-level Talents of Guizhou Institute of Technology
- Shanghai Advanced Research Institute, Chinese Academy of Sciences
- Institute of Molecular Medicine, School of Medicine, Shanghai Jiao Tong University