Yang Qijing, Sun Xiaolin, Ding Qihang, Qi Manlin, Liu Chengyu, Li Tingxuan, Shi Fangyu, Wang Lin, Li Chunyan, Kim Jong Seung
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.
Natl Sci Rev. 2024 Jun 26;11(8):nwae225. doi: 10.1093/nsr/nwae225. eCollection 2024 Aug.
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. 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.
牙周炎涉及过度活化的基质细胞，这些细胞招募免疫细胞，加剧炎症。本研究展示了一种设计用于治疗牙周炎的ATP响应性金属有机框架（Mg/Zn-MOF），利用离子干扰来调节免疫反应并防止组织破坏。针对传统免疫调节纳米材料面临的协同离子效应和靶向递送挑战，Mg/Zn-MOF系统由细胞外ATP激活——牙周炎病理过程中的关键分子——确保靶向离子释放。从框架中释放的镁离子和锌离子通过减弱Gasdermin D（GSDMD）的表达和激活，协同抑制膜孔形成。这一作用减少了细胞焦亡、乳酸脱氢酶和IL-1β的释放，阻止了炎症级联反应的发生。从机制上讲，Mg/Zn-MOF干预NLRP3/Caspase-1/GSDMD和Caspase-11/GSDMD两条途径以减轻细胞焦亡。评估证实其在减少炎症细胞浸润和保持胶原完整性方面的有效性，从而防止牙周组织损伤和骨质流失。这项研究突出了离子干扰策略在牙周炎免疫治疗中的前景，代表了在开发靶向治疗方法方面的重要进展。
