首页|An ATP-responsive metal-organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis

An ATP-responsive metal-organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis

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Periodontitis involves hyperactivated stromal cells that recruit immune cells,exacerbating inflammation.This study presents an ATP-responsive metal-organic framework(Mg/Zn-MOF)designed for periodontitis treatment,utilizing ion interference to modulate immune responses and prevent tissue destruction.Addressing the challenges of synergistic ion effects and targeted delivery faced by traditional immunomodulatory nanomaterials,the Mg/Zn-MOF system is activated by extracellular ATP-a pivotal molecule in periodontitis pathology-ensuring targeted ion release.Magnesium and zinc ions released from the framework synergistically inhibit membrane pore formation by attenuating Gasdermin D(GSDMD)expression and activation.This action curtails pyroptosis,lactate dehydrogenase and IL-1β release,thwarting the onset of inflammatory cascades.Mechanistically,Mg/Zn-MOF intervenes in both the NLRP3/Caspase-1/GSDMD and Caspase-ll/GSDMD pathways to mitigate pyroptosis.In vivo assessments confirm its effectiveness in diminishing inflammatory cell infiltration and preserving collagen integrity,thereby safeguarding against periodontal tissue damage and bone loss.This investigation highlights the promise of ion-interference strategies in periodontitis immunotherapy,representing a significant stride in developing targeted therapeutic approaches.

metal-organic frameworkperiodontitispyroptosisimmunotherapyion-interference therapy

Qijing Yang、Xiaolin Sun、Qihang Ding、Manlin Qi、Chengyu Liu、Tingxuan Li、Fangyu Shi、Lin Wang、Chunyan Li、Jong Seung Kim

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Department of Prosthodontics,Jilin Provincial Engineering Laboratory of Intelligent Oral Treatment Technology,School and Hospital of Stomatology,Jilin University,Changchun 130021,China

Department of Chemistry,Korea University,Seoul 02841,South Korea

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaKey Program of Natural Science Foundation of Jilin ProvinceKey Program of Natural Science Foundation of Jilin ProvinceKey Program of Natural Science Foundation of Jilin ProvinceKey Program of Natural Science Foundation of Jilin ProvinceFunding of Jilin Province Development and Reform CommissionFunding of Jilin Province Development and Reform CommissionScience and Technology Project of Jilin Province Financial DepartmentGeneral Program of China Postdoctoral Science FoundationNational Research Foundation of KoreaFundamental Research Funds for the Central Universities

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2024

10.1093/nsr/nwae225

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ISSN：
年,卷(期)：2024.11(8)