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

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外文摘要：Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microen-vironment,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 re-sults demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype(i.e.,from-M l-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 mac-rophages while enhancing oxidative phosphorylation(OXPHOS),facilitating the shift from Ml to M2 macrophage subtype.Our findings suggest that Q@MPDA is a promising treatment for periodontitis via immunometabolic rewiring.

外文关键词：

QuercetinPeriodontitisMacrophageGlycolysisOxidative phosphorylation(OXPHOS)Mesoporous polydopamineMitochondrial reactive oxygen speciesImmunometabolic rewiring

作者：

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

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作者单位：

Department of Implant Dentistry,Shanghai Ninth People,s Hospital,Shanghai Jiao Tong University School of Medicine,College of Stomatology,Shanghai Jiao Tong University,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Shanghai Key Laboratory of Stomatology,Shanghai 200011,China

State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

Zhongshan Institute for Drug Discovery,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Zhongshan 528437,China

NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,Shanghai 201203,China

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出版年：

2024

DOI：

10.1016/j.apsb.2024.07.008

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(11)