김종승 (고려대학교)

한빛사논문

조회87

고려대학교

Natl. Sci. Rev., Aug 2024, 11 (8) nwae225 | https://doi.org/10.1093/nsr/nwae225 An ATP-responsive metal-organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis

Qijing Yang^1,†, Xiaolin Sun^1,†, Qihang Ding^1,2,†, Manlin Qi¹, Chengyu Liu¹, Tingxuan Li¹, Fangyu Shi¹, Lin Wang^1,∗, Chunyan Li^1,∗and Jong Seung Kim^2,∗

¹Department of Prosthodontics, Jilin Provincial Engineering Laboratory of Intelligent Oral Treatment Technology, School and Hospital of Stomatology, Jilin University, Changchun 130021, China and

²Department of Chemistry, Korea University, Seoul 02841, South Korea

^∗Corresponding authors : Lin Wang, Chunyan Li, Jong Seung Kim

^†Equally contributed to this work.

Abstract

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-11/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.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-09)
연구진국내(교신)+국외 연구진
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