Mitochondrial Calcium Ion Nanogluttons Alleviate Periodontitis via Controlling mPTPs

作者全名："He, Ping; Liu, Fengyi; Li, Mingzheng; Ren, Mingxing; Wang, Xu; Deng, Yangjia; Wu, Xianghao; Li, Yuzhou; Yang, Sheng; Song, Jinlin"

作者地址："[He, Ping; Ren, Mingxing; Wang, Xu; Deng, Yangjia; Wu, Xianghao] Chongqing Med Univ, Coll Stomatol, Chongqing 401147, Peoples R China; [Liu, Fengyi; Li, Mingzheng; Li, Yuzhou; Yang, Sheng; Song, Jinlin] Chongqing Med Univ, Stomatol Hosp, Chongqing 401147, Peoples R China; [Liu, Fengyi; Li, Mingzheng; Li, Yuzhou; Yang, Sheng; Song, Jinlin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 401147, Peoples R China; [Liu, Fengyi; Li, Mingzheng; Li, Yuzhou; Yang, Sheng; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 401147, Peoples R China"

通信作者："Yang, S; Song, JL (通讯作者)，Chongqing Med Univ, Stomatol Hosp, Chongqing 401147, Peoples R China.; Yang, S; Song, JL (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 401147, Peoples R China.; Yang, S; Song, JL (通讯作者)，Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 401147, Peoples R China."

来源：ADVANCED HEALTHCARE MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000954960800001

JCR分区：Q1

影响因子：10

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：macrophages; mitochondrial calcium ions; mitochondrial permeability transition; nanoparticles; periodontitis

摘要："The mitochondrial permeability transition (mPT) directly affects mitochondrial function in macrophages. Under inflammatory conditions, mitochondrial calcium ion (mitoCa(2+)) overload triggers the persistent opening of mPT pores (mPTPs), further aggravating Ca2+ overload and increasing reactive oxygen species (ROS) to form an adverse cycle. However, there are currently no effective drugs targeting mPTPs to confine or unload excess Ca2+. It is novelly demonstrated that the initiation of periodontitis and the activation of proinflammatory macrophages depend on the persistent overopening of mPTPs, which is mainly triggered by mitoCa(2+) overload and facilitates further mitochondrial ROS leakage into the cytoplasm. To solve the above problems, mitochondrial-targeted ""nanogluttons"" with PEG-TPP conjugated to the surface of PAMAM and BAPTA-AM encapsulated in the core are designed. These nanogluttons can efficiently ""glut"" Ca2+ around and inside mitochondria to effectively control the sustained opening of mPTPs. As a result, the nanogluttons significantly inhibit the inflammatory activation of macrophages. Further studies also unexpectedly reveal that the alleviation of local periodontal inflammation in mice is accompanied by diminished osteoclast activity and reduced bone loss. This provides a promising strategy for mitochondria-targeted intervention in inflammatory bone loss in periodontitis and can be extended to treat other chronic inflammatory diseases associated with mitoCa(2+) overload."

基金机构："National Natural Science Foundation of China [U22A20314, 82171010]; Natural Science Foundation of Chongqing [cstc2021jcyj-jqX0028]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0079]; National Key R&D of Program of China [2022YFC2504200]; Project of Chongqing Graduate Tutor Team [dstd201903]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (Grant No. 82171010), the Natural Science Foundation of Chongqing (Grant No. cstc2021jcyj-jqX0028), Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0079), National Key R & D of Program of China (Grant NO. 2022YFC2504200), National Natural Science Foundation of China (Grant No. U22A20314), and Project of Chongqing Graduate Tutor Team (dstd201903)."