Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS

作     者：Yi Zhang Junyu Shi Jie Zhu Xinxin Ding Jianxu Wei Xue Jiang Yijie Yang Xiaomeng Zhang Yongzhuo Huang Hongchang Lai 

作者机构：Department of Implant DentistryShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai 200011China State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Zhongshan Institute for Drug DiscoveryShanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan 528437China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical ExcipientsShanghai 201203China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2024年第14卷第11期

页      面：5026-5036页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：National Key Research and Development Program of China(2022YFE0203600,China) National Nature Science Foundation of China(82271028,82341232) Department of Science and Technology of Guangdong Province(High-level New R&D Institute 2019B090904008,High-level Innovative Research Institute 2021B0909050003,China) Zhongshan Municipal Bureau of Science and Technology(LJ2021001&CXTD2022011,China) It also supported by the Project of Biobank(YBKB202102,China) Research Discipline Fund(KQYJXK2020,China) Cross-disciplinary Research Fund(JYJC202205,China)from Shanghai Ninth People's Hospital(SHSMU-ZDCX20212500,China) Shanghai Pujiang Program(22PJD038,China) 

主　　题：Quercetin Periodontitis Macrophage Glycolysis Oxidative phosphorylation(OXPHOS) Mesoporous polydopamine Mitochondrial reactive oxygen species 

摘      要：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.e., 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-1β and TNF-α) 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 via immunometabolic rewiring.